Kitabı oku: «The Power Of Youth. How To Tune Our Mind And Body For A Long And Healthy Life»

Project Manager Yu. Semenova

English proofreader K. Akhmetov

Computer layout by N. Astakhova

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© A. Fomenko, 2023

© Alpina PRO LLC, 2023

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INTRODUCTION

IS IT POSSIBLE TO LIVE 100 YEARS? MANY WOULD ANSWER THAT IT'S GOOD ENOUGH TO REACH AT LEAST THE AGE OF 80, BUT TO LIVE A CENTURY IS RATHER AN EXCEPTION TO THE RULE AND A CHANCE THAT ONLY LUCKY ONES GET.

But what if it is far from that? There is a more optimistic scenario, which extrapolates: living to 100 or more and staying healthy and active is a real possibility for everyone.

It is almost everyone's biggest dream to live a long life. But various age-related problems, manifested in the form of physical weakness, mental decline, developing diseases, and other pathological changes, can block the path to this dream. Usually, all the average person can do to avoid it is to start exercising, quit using harmful substances, change their diet to include more healthy products, and try to avoid contact with infections. This is certainly important. But is it enough?

There is a lot of information nowadays about different ways to delay aging and prolong life. Theories, reviews, perspectives, and research findings we receive from paper and digital sources are varied, not all of them congruent, but often contradictory. There are lots of opinions on whether fasting is good for the body, what diet is the most effective, how much exercise we need, whether we should take vitamin supplements, how much time we should spare to get a daytime sleep, etc. Search engines "answer" these and other questions with millions of links.

But what if it comes to the prolongation of life and youth? Some specialists would say that if you want to live a long life, you need to strictly follow the laws of a healthy lifestyle; others would say that it is necessary to take as many geroprotectors¹ as possible; still, others would insist on continuous monitoring of health outcomes: measure physiological data and take regular tests. When it comes to our health, how not to get lost in the informational flow and ignore the unnecessary? What should we rely on?

Existing approaches to the problem of aging and prolongation of life are often flawed and rather one-sided. We should keep in mind that the problem is larger than it appears, so we need to consider it more broadly and consider many views. There are many ways to live a long life, and we will find out which of them are the most effective.

This book is a kind of "encyclopedia of aging" – it contains all the most important things you need to know about this process, as well as ways to prolong life and youth. Here you will find all the information about aging mechanisms, how to slow it down, how to prevent age-related diseases, and the lifestyle and mindset of long-livers.

After reading this book, you will gain the knowledge to acquire extra years of life, and you will learn how to apply them in practice, i.e., turn them into skills to control and even manage all physiological changes to achieve better health and longevity.

The knowledge gathered here comes from years of work on the VSH25² project. Its goal is not just to prolong life, but to preserve youth and stop aging with an experimental biological program.

There are a lot of long-living animals and plants in the world, from turtles and sharks that live hundreds of years to baobabs and sequoias that live thousands of years. Some do not age at all. The attention of biologists and gerontologists has been drawn to naked mole rats for decades: these small rodents live an unusually long time compared to their relatives, and at the same time practically do not age or get sick. Another phenomenon is the jellyfish Turritopsis dohrnii: it can live forever. At maturity or under adverse conditions, this animal can "go back to childhood" – to the very first stage of the life cycle, which makes the jellyfish immortal.

Humans do not live that long compared to the record-breakers of wildlife. Before the twentieth century, the average life expectancy was about 40 years. However, this figure was almost doubled, and now, according to official data, it is about 73 years old. This happened not only due to medical advances, but also because the consciousness of mankind is gradually shifting, and the idea of life prolongation is more and more actively embodied in life. In the XXI century, new futuristic projections suggest a life expectancy of 150 and even 200 years.

Science and medicine have taken a great step towards understanding mechanisms underlying longevity, and so many discoveries lie ahead! Future breakthroughs in rejuvenation, gene therapy, stem cells, regenerative medicine, and organ replacement will one day allow people not to age or have a finite lifespan.

Living as long as possible is a goal that humanity shall give top priority. At the same time, each needs to remain motivated to maintain their health and prolong life: to learn about new medical advances, to read more on these topics, including materials on various scientific areas – even those, not obvious ones, such as mathematics and physics. Because knowing such universal concepts as brain, body, consciousness, time, evolution, death, and immortality will help to look at the problem of life prolongation from a completely different angle and to think about other scenarios for human development.

It is important to prolong not only life but youth – even if a third of the people on the planet do it, the world will change for the better. It is not a fantasy or an elusive goal. There is no need for lots of energy-consuming efforts or expensive means. All you need is to realize the responsibility for yourself and your life, understand how to "turn on" the body's defenses, and maintain the desire to live long, learning about new advances in the world of science and medicine.

SCIENTISTS HAVE PROVED

1. EXPECTATION OF LIFE PROLONGATION IS ALREADY PROLONGING LIFE.

2. OPTIMISTIC PEOPLE LIVE LONGER AND ARE LESS LIKELY TO SUFFER FROM PAIN. SADNESS AND DISSATISFACTION WITH LIFE CAN SHORTEN IT BY 13 YEARS (AS WELL AS SERIOUS HEALTH ISSUES).

3. MEANINGFUL EXISTENCE PROLONGS LIFE.

4. A SUBJECTIVE FEELING OF OUR AGE PROLONGS LIFE.

5. THERE ARE CURRENTLY NO PROVEN OR APPROVED ANTI-AGING DRUGS IN THE WORLD.

6. PLACEBO WORKS EVEN WHEN A PERSON KNOWS IT IS A PLACEBO.

7. THE EFFECTIVENESS OF A PLACEBO COMPARED TO MEDICATIONS IS INCREASING.

8. THE EFFECTIVENESS OF A PLACEBO IS INCREASING IN DEVELOPED COUNTRIES.

9. MANY MEDICATIONS HAVE ALMOST THE SAME EFFECT AS A PLACEBO, BUT ALSO CREATE SIDE EFFECTS.

10. EXPECTATION TO FEEL BETTER AFFECTS THE SYMPTOMS OF A DISEASE.

11. WE CAN "TURN ON" THE NECESSARY GENES AND "TURN OFF" THE UNNECESSARY ONES.

12. 95 % OF DISEASES CAN BE AFFECTED BY THE PERSON.

13. SPIRITUAL PRACTICES HELP US FEEL HAPPY AND HEALTHY.

14. THE QUANTITY AND QUALITY OF SOCIAL TIES AFFECT LIFE SPAN.

15. CONCENTRATION OF ATTENTION IS AN IMPORTANT SKILL TO ACHIEVE ANY GOAL, INCLUDING PROLONGATION OF LIFE AND YOUTH.

16. HABITS AFFECT OUR LIVES AND OUR PHYSICAL AND MENTAL CONDITION.

17. MOST THINGS WE DO UNCONSCIOUSLY. THEREFORE, THE FORMATION OF USEFUL HABITS AFFECTS 90 % OF OUR ACTIONS AND LEADS TO A QUALITATIVE CHANGE IN ALL LIFE.

18. PASSION FOR ART HELPS PROLONG LIFE BY 30 %.

19. CONSCIENTIOUS PEOPLE LIVE LONGER SINCE THEIR IMMUNE SYSTEM WORKS BETTER (DUE TO LOW LEVELS OF B-CELL STIMULATORY FACTOR 2).

20. THE THOMAS THEOREM SAYS: "IF MEN DEFINE SITUATIONS AS REAL, THEY ARE REAL IN THEIR CONSEQUENCES."

CHAPTER 1
AGING AND YOUTH

THE DREAM OF A LONG LIFE IS MEANINGLESS WITHOUT RESOLVING THE AGING PROBLEM – MEMORY IMPAIRMENT (OR COMPLETE MEMORY LOSS), WORSENING FRAILTY, NEED FOR CONTINUOUS CARE, A BUNCH OF AGE-RELATED DISEASES, HUGE NUMBER OF MEDICATIONS TO SUPPORT A FADING BODY, ETC.

Such prospects do not please anybody. At the same time, we can look at aging from essentially different points of view. You can resign yourself, and take age-related decline and diseases as an inevitability and part of human destiny. However, there is another point of view. Just look at people who live longer than others having a healthy, strong body, a clear mind, and a zest for life. We might wonder how they do it. To find the answer, it is very important to get onto aging, and scientific views about the nature of this phenomenon. And then to learn about studies revealing mechanisms of preserving youth and increasing longevity.

WHAT BODY CHANGES ARE CAUSED DUE TO AGING?

As a person grows older, their appearance, health, and the function of most organs change. The set of these metamorphoses, which manifest both externally and internally, is called aging. Here are some signs characteristic of aging.

● Hearing impairment: children can hear high-frequency sounds (above 20 Hz) – this ability is usually lost by the end of adolescence. After age 75, more than half of older adults hearing gets worse so much that it prevents normal communication.

● Vision problems: after the age of 35, the tone of the ciliary muscle, responsible for accommodation³ (change in the curvature of the lens) decreases. As a result, farsightedness (presbyopia) develops and progresses after the age of 40 – a deterioration in the ability to see near objects. In addition, over the years, the risk of cataracts (clouding of the lens) increases.

● Change in skin tone: due to lower production of hyaluronic acid, collagen, and elastin fibers over the years, the skin loses elasticity, which leads to wrinkles.

● Over the years, the function of cells producing melanin, the substance that determines hair color, suffers, and graying comes with this process. In addition, as we age, our hair begins to fall out more actively, and the risk of alopecia (hair loss) increases.

● As we age, we lose muscle mass and strength, and muscle's ability to regenerate deteriorates.

● After the age of 25, fertility (ability to conceive) in women starts to decline. At the age of 44 to 55 years, (there can be deviations in either direction) menopause occurs, and loss of the ability to childbirth. Men's sexual function also deteriorates over the years, increases the risk of erectile dysfunction, and decreases the fecundating ability.

● Cognitive function often deteriorates over the years: learning and memory deficit, the risk of dementia, including Alzheimer's and Parkinson's disease, increases.

● There is a higher risk for several diseases: osteoporosis (brittleness of the bones), osteoarthrosis, atherosclerosis, hypertension, obesity, diabetes, coronary heart disease, cerebrovascular disease, cancer, immune deficiency, etc.

In addition to symptoms of aging, changes at the cellular and molecular levels develop with age, and it has an impact on our bodies. Scientists from the Department of Biochemistry and Molecular Biology at the University of Oviedo (Spain) state that aging is based on the following biological processes⁴.

● Accumulation of mutations in cells (genomic instability), which increases the risk of developing diseases and malignant tumors.

● Shortening of telomeres, end sections of chromosomes, that protect genetic material from damage. It also causes errors in the genome, protein production, and dysfunction of cell and organ function.

● Accumulation of so-called senescent cells, incapable of division or apoptosis (planned cell death leading to tissue renewal). Such cells do not die, but partially or completely lose their functions, leading to organ malfunction.

● Decreased sensitivity of cells to "positive" growth factors, and hormones, activating energy exchange in cells, which stimulate regeneration. At the same time, the sensitivity of cells to the action of damaging factors, such as radiation, toxic substances, antibiotics, etc., increases with age.

● Depletion of stem cells, which are "samples" for functional cells of various organs.

● Deterioration of intercellular communication, signaling between cells, which ensures a coordinated work of the body.

There is such a concept as biomarkers of aging – a set of physiological and biochemical indicators, that allow us to judge the biological age of a person. A table listing the basic biomarkers of aging is given at the end of the chapter.

THEORIES OF AGING

Although since antiquity, humans have tried to understand what biological aging is and how to prevent it, scientists have not yet come to a common understanding of the nature of aging. Today there are many theories explaining the reasons for the physical and mental decline that occurs with age. All these theories can be divided into two large categories: damage theories and evolutionary theories – theories of programmed aging⁵.

AGING AS A PROCESS PROGRAMMED BY NATURE

Evolutionary theories of aging imply that aging is the result of the organism following a biological "schedule" regulating the main stages of human life: birth, growth and development, growth impairment, stagnation, biodegradation, and death. In the view of advocates of this approach, aging gives an advantage in the survival of a particular population and is evolutionary "beneficial" for species. In the first place, it is about resource allocation: individuals who have lost their reproduction capability shall age and die in order not to compete for resources with the younger generation.

There are some examples of the evolutionary theories of aging.

● Theory of programmed longevity. Throughout life, certain genes are "turned on" and others are "turned off" by nature, i.e., regulation of aging processes is embedded at the DNA level.

● Neuroendocrine theory. It suggests that aging is an impaired hormonal balance. This theory appeared in the XIX century, and in the early XX century experiments on transplanting various endocrine glands (ovaries and testicles, adrenal glands, basal glands) from young animals to elderly ones became popular. Today, some scientists associate aging with changes in insulin and insulin-like growth factor (IGF) signaling⁶.

● Immunologic theory of aging. It views aging as a consequence of an evolutionarily programmed process of "immunological decline" that occurs with age. The efficiency of immunity peaks during adolescence. The ability to resist infections, destroy harmful microbes, identify mutated cells, and respond to vaccines, decreases over the which makes the body vulnerable to the negative joint action of external and internal factors, leading to disease and death. One of the key aspects underlying immunologic aging is the immunosenescence⁷ – age-related changes in the thymus gland responsible for training immune cells⁸.

AGING AS A RESULT OF DAMAGE (ERRORS) ACCUMULATION

While supporters of "programmed aging" theories view age-adverse changes as the result of an inevitable evolutionary program, followers of "damage theory" do not consider aging a "genetic doom." They believe that the body accumulates many "breakdowns" with age due to the influence of external factors, stress, etc. A gradual accumulation of such damages leads to the development of age-related diseases and, eventually, to death.

There are examples of damage accumulation theories.

● DNA damage theory. During cell division and copying of DNA molecules, there is always a risk of genetic errors (mutations) that accumulate with age and result in age-related diseases, primarily malignant tumors. In addition, adverse mutations, accumulating with age, can occur under the influence of factors external to the cell: ultraviolet radiation, virus entry, inserting their genome into hereditary material, etc.⁹.

● Genetic instability theory. It is not about mutations associated with damage, but rather about various changes in the genome occurring in the chromosome division. For example, such things as aneuploidy, the presence of an abnormal number of chromosomes in a cell, are identified in the fetal brain at all stages of intrauterine development. After birth, the number of such neurons decreases significantly, but some of them remain and can cause brain cancer¹⁰.

● Free radical theory. Supporters of this theory affirm that free radicals (particles, containing oxygen with one missing electron) are the cause of cellular malfunction. They are needed for many biochemical processes and are constantly formed in the body during breathing. By leaving the place where they needed, they sort of "take" an electron from the body, and this is called an oxidative reaction. Free radicals are a serious threat to cell activity because they damage proteins and lipids¹¹.

Among the numerous theories of aging today, the following concepts are also emphasized.

● Apoptosis theory. Body tissues are constantly updated: "worn-out" cells whose function is deteriorating, as well as cells damaged by infection, having genetic mutations, regularly commit "suicide." Programmed cellular self-destruction is called apoptosis. In Greek, ἀπόπτωσις means "leaf fall": old cells die, like autumn leaves, to make way for the younger generation. There is an apoptosis gene in the DNA of each cell that triggers cellular self-destruction in response to molecular signals. The problem is that over the years, the sensitivity of cells to signals, activating their "suicide," decreases, leading to an accumulation of damaged, low-functioning cells. The aging process is based on the decreased ability of tissues to remove aged cells¹².

● Elevational (ontogenetic) theory of aging. In the mid-twentieth century, the Soviet gerontologist V. M. Dilman related aging and ontogeny¹³ (individual development) of the homeostatic systems of the organism. The scientist named an elevation in the hypothalamus sensitivity threshold – the "conductor" of an endocrine system – to homeostatic signals as the key mechanism of aging. In a series of experiments, it was proved that this mechanism is based on the adverse changes in the reproductive, hypothalamic-pituitary-adrenal axis, which provides the necessary number of glucocorticoids in the blood (the so-called stress hormones) and increases their secretion under stress, which eventually leads to hyperadaptosis, i.e., a condition of excessive body adaptation to stress. The same mechanism in the metabolic homeostasis system causes the accumulation of body fat, a decrease in tissue sensitivity to insulin, and the development of atherosclerosis. Dilman found that age-related transformations occurred because of homeostatic ontogenesis, creating conditions for the formation of malignancies. Thus, the scientist concluded that aging is not programmed, but is a byproduct of the genetic developmental program. This led to the belief that aging can be slowed down if homeostasis is stabilized at the level achieved by the end of the organism's development.

● Telomere theory of aging. The number of divisions of each cell in the body is limited. This is because the protective structures at the ends of chromosomes, called telomeres, shorten with each cell division¹⁴. Telomere shortening may be a molecular "clock" triggering aging. It was found that the enzyme telomerase, which protects telomeres from shortening, is actively produced in cancer cells, that can divide almost infinitely. Telomerase activity has been detected in more than 85 % of malignant tumors, whereas it is absent in cells of healthy tissues¹⁵.

● Inflammatory theory of aging. This concept intersects with the immunologic theory of aging, but the priority here is given to the overblown immune response to various factors, including autoimmune responses – "aggression" directed at one's tissues – and not on the loss of the ability to fight off infections and recognize mutations. Under this theory, which is considered one of the most relevant today, aging is a general inflammatory process affecting all organs. It is inflammation that underlies the development of such age-related diseases as atherosclerosis, Alzheimer's disease, cardiovascular disease, diabetes mellitus type II¹⁶.

We told only some theories of aging – there are many more. This large number of views on the causes and nature of age-related changes demonstrates the lack of a unified understanding of the process. It also suggests that aging is based not on a single mechanism, affecting which could indefinitely prolong youth, but on a complex set of causes operating at the genetic, molecular, and evolutionary levels. The multifactorial nature of aging helps us to understand that prevention of aging shall also be comprehensive and diversified.

HEALTHY LIFESTYLE HELPS TO SLOW DOWN AGING

A healthy lifestyle has many definitions, but all scientists agree on one trend: it is a way of living aimed to maintain and improve health, both physical and mental. And firstly, people themselves are responsible for their well-being: they must have the knowledge and skills, as well as be active in achieving the goal of being healthy.

A healthy lifestyle is a combination of many healthy habits (and rejection of bad ones, such as smoking, drinking abuse, etc.). The effectiveness of some aspects of a healthy lifestyle to prevent aging has been confirmed by many studies.

1. PHYSICAL ACTIVITY. Exercise is seen as a beneficial stress for the body, positively affecting various aspects of physiology. It is proved that moderate stress caused by physical activity slows down the skeletal muscles aging¹⁷, activates the antioxidant systems of the body¹⁸, normalizes metabolic processes¹⁹, stimulates the formation of somatotropic hormone (growth hormone), which significantly accelerates regeneration processes in the body²⁰, helps normalize blood pressure levels and reduces the risk of hypertonia²¹.

FUN FACT

TO REDUCE THE RISK OF PREMATURE DEATH, IT IS ENOUGH TO JUST STAND MORE DURING THE DAY.

A study conducted by scientists from UCLA School of Medicine found that older people who spent more time standing had a 37 % lower risk of death compared to those who sat more often during the day. The longest "standing" time among the subjects was about 90 minutes a day, but it turned out that even half an hour spent in an upright stance allow achieving the desired effect.

2. BREATHING EXERCISES. Breathing is essential to the functions of the body. But do we breathe right? If we do not pay enough attention to this important process, and breathe frequently and intermittently, as it happens unknowingly, it causes dysfunction of the internal organs, and major health problems – from insomnia to atherosclerosis. To avoid this, it is essential to be able to do breathing exercises. Read more in Chapter 13.

3. CALORIE RESTRICTION. The idea that a caloric deficit can prolong life comes from theories connecting longevity and metabolic rate. The authors and defenders of these theories believe that living beings are given a limited number of resources, including energy, which can be expended during life. Restricting caloric intake, leading to a slowing down of metabolic processes, helps to save "life force": figuratively speaking, a fire will burn longer if we toss small portions of fuel into it. There is evidence for the accuracy of such a view.

4. SLEEP CULTURE. According to the National Sleep Foundation, adults need 7 to 9 hours of sleep per night²². Young children need more hours to grow and develop (the younger the child, the more). People over the age of 65 need 7 to 8 hours of sleep.

Getting enough hours of sleep and monitoring its quality are two important aspects for those who want to achieve longevity and maintain their health. Sleep gives energy for mental and physical activity, contributes to the recovery processes, and strengthens almost all systems of the body.

Experts recommend always following a sleep regime, even on weekends, performing relaxing treatments before going to bed (for example, meditating, reading, taking a hot bath), avoiding caffeine or alcohol several hours before bedtime, choosing a comfortable quality mattress and pillow, maintain an optimal temperature and pleasant aroma in the bedroom, turn off lights and electronic devices (TV, computer, smartphone, etc.) an hour before bedtime.

Find out if you suffer from apnea (pauses in breathing during sleep), one of the most common causes of poor sleep. It increases the risk of high blood pressure and heart disease.

5. HEALTHY MIND. A healthy lifestyle is not just about exercising or dieting. It is also a concern for mental well-being and the development of cognitive skills. Such components of a healthy lifestyle as a positive attitude to life, stress management, and intellectual discipline (reading, language learning, and logic games), play a key role in maintaining mental health and increasing life expectancy.

One of the most effective methods to "free the mind" is meditation. It helps to shift attention from worrying about the future or fixing the past to the present moment and thus helps to interrupt the endless flow of negative thoughts and anxiety. You do not need to play appropriate music or light incense (this is optional) to start meditating, just find a quiet place and take a comfortable position. You can learn the meditation process yourself. For example, with the help of dedicated apps.

6. FEELING YOUNGER. Although health deterioration in the aging process is universal, people perceive and experience it in different ways. Scientists from Seoul National University, together with colleagues from Yonsei University (South Korea), concluded that feeling younger than you are is a major component of good health in mature years²³. But the subjective feeling of being older, as MRI has shown, on the contrary, reflects a more rapid brain aging. This has also been confirmed by French and American scientists²⁴. The study involved 17,000 retirement-age people who were followed for 20 years. It turned out that subjects who felt 8-13 years older had an increased risk of early death (by 18–25 %).

7. GREATER SOCIAL TIES. It is almost impossible to keep track of long life without diseases alone, without the motivating force of family, friends, and loved ones. You can only do it with people supporting you. A person has a great opportunity to generate more resources, energy, and experience together with other people, which will necessarily affect not only the general quality of life but also the internal physiological and mental condition.

8. GOAL SETTING. People who know why they live have the best chance to live longer. Many studies confirm this hypothesis. Having a purpose in life is characteristic of the inhabitants of the so-called "longevity regions" – places where people on average live longer than the population of the Earth. Dan Buettner, an American writer, and traveler, calls such places "blue zones." In a series of books on features of life in these amazing areas, Buettner points out that almost all blue zone inhabitants have special mindfulness practices allowing them to find meaning in life.

The inhabitants of the Japanese island of Okinawa have a practice called ikigai. This is translated as "something or someone that gives a person a sense of purpose or a reason for living." It is a person's main interest, the main aspiration in life. It answers the questions like "What am I doing here?" – "Why am I living?" – "How can I be useful to the world?" etc. Ikigai is a comprehensive notion running through life and helping to find yourself, your path, meaning, and purpose.

The inhabitants of another blue zone, the Nicoya Peninsula in Costa Rica, believe that a plan de vida is essential for a long, happy life. This term means a constant search for a reason to wake up in the morning, to enjoy every single day.

CONCLUSION

It is everyone's dream to live in a young body as long as possible. There is no universal recipe, practice, or panacea that can solve the problem of aging and premature death once and for all. The way to this dream is through the formation of many habits: sufficient physical activity, adequate nutrition, healthy sleep, as well as mindfulness practices allowing to boost optimism and define life goals.

And it does not matter which view of aging dominates now – the "program" written in the genes, or the random accumulation of "breakdowns." Indeed, these theories allow us to understand some patterns and build a safety net in dangerous moments. At the same time, research shows that the main levers for managing life and youth prolongation are in our hands. That is why each of us can now take responsibility for our own lives and begin to create our own "blue zone."

BIOMARKERS OF AGING

CHAPTER 2
GENETICS

GENETICS IS EVOLVING MORE RAPIDLY: EACH YEAR OF DNA RESEARCH BRINGS MORE DISCOVERIES THAN THE PREVIOUS ONE. THIS SCIENCE HAS SPREAD TO MEDICINE, PSYCHOLOGY, ANTHROPOLOGY, ECOLOGY, AND OTHER FIELDS. IT HAS BECOME THE BASE FOR UNDERSTANDING THE HUMAN NATURE. GENETICS STUDIES THE BASIC MECHANISMS OF HEREDITY AND VARIABILITY, PROPERTIES THAT ARE COMMON TO ALL ORGANISMS. IT HOLDS GREAT PROMISE FOR PROLONGING A HEALTHY AND ACTIVE LIFE.

DEVELOPMENT OF GENETICS

Even though genetics as a science was formed only in the XX century, our remote ancestors had some understanding of heredity. Even thousands of years ago, people knew that certain traits could be passed from one generation to the next. Considering this, they crossed and bred animals and plants, improving their properties and functions.

The first and simplest assumption of how certain traits are inherited was that the traits of both parents are "mixed" in the children, so the children are something between the mother and the father. However, already ancient Romans knew that this process had to take place differently.

In the mid-nineteenth century, the experiments of the Austrian friar Gregor Mendel made us closer to the modern understanding of the memory of generations. The examples from his observations of plants showed that traits are not mixed, but are transmitted in the form of discrete (isolated) units to the next generations. The scientific community did not attach great importance to his discovery.

Only in 1900 did botanists Hugo de Vries, Carl Erich Correns, and Erich Tschermak obtain similar to Mendel's results and, one after another, published studies that confirmed his hypothesis. In 1909, Danish biologist Wilhelm Johannsen called the discrete units responsible for the transmission of traits "genes", and in 1910 American geneticist Thomas Hunt Morgan established that genes are located in chromosomes. Scientists were able to explore the function of chromosomes only in the middle of the twentieth century when it turned out that hereditary information is contained in DNA.

Less than 70 years have passed since James Watson, Francis Crick, and Rosalind Franklin deciphered the structure of DNA. Since then, many discoveries have been made on the structure of the human body and using this information to prolong life. And for that, we must take a closer look at what DNA is.

OUR GENETIC CODE

Deoxyribonucleic acid (DNA), which is found inside the nucleus of every cell, holds the information that makes an organism what it is. To understand what it looks like, you can imagine a zipper twisted into a spiral. This long spiral chain, consisting of two strands, is constructed of four blocks called nucleotides: adenine – A, cytosine – C, guanine – G, and thymine – T. The entire DNA "text" consists of about six billion "letters" and contains "instructions" for the construction of every cell in our body. Each of the nucleotides has a pair from another strand, to which it is joined by hydrogen bonds. Adenine will always be paired with thymine and cytosine with guanine.

Regions of nucleotide sequences are called genes. The set of genes received at birth is the genotype, and all hereditary material contained in a cell is called a genome.

Proteins are the levers by which DNA controls the body. They are necessary for various biochemical reactions (as catalysts), metabolism, digestion, wound healing, etc. – for all the complex physiological interaction that ensures the health and life of the body. Proteins are formed during gene expression, the conversion of the hereditary information located in genes.

Expression occurs in several stages, but the key ones are transcription and translation. When the cell needs a certain protein – the transcription starts, i.e., the sequence of nucleotides in the right part of the DNA is copied into the ribonucleic acid (RNA). These RNA copies of DNA fragments act as matrices for protein synthesis – the translation starts.

The information flow in cells is directed from DNA to RNA, from RNA to protein – this is the central dogma of molecular biology.

The global Human Genome Project, completed in 2003, found that there are about 22,000 genes encoding proteins in human cells. Quite interesting, because before it was supposed to be at least 100 thousand. But it turned out that humans do not need so many genes, because each of them can perform several functions at once and synthesize several protein variants.

Except for the coding DNA, there is also non-coding DNA in the cell – the one that does not synthesize proteins. It makes up about 98 % of all human DNA. It is often called "junk DNA," because it is not yet fully understood exactly what functional activity non-coding DNA has. However, despite its name, it is also important for the life of the organism, and part of it plays a role in epigenetic (remember this word) regulation.

It can be said that genes are essentially eternal. Each of the DNA molecules can control its reproduction: copy itself and continue to exist for millions of years. But genes can change – various conditions affect them – and human health depends on these changes (mutations) because they are the root cause of many diseases.

GENETICS AND MEDICINE

Human genes are like little computer programs, embedded in humans since ancient times. For example, tens of thousands of years ago the insulin receptor gene in adipose tissue made sense for our ancestors: it helped to store as many calories as possible at a time when food was always in short supply. Today, however, humans have no need to forget hunger, so the gene does more harm than good: problems such as overweight and obesity develop at double speed. The modern computer age requires humans to update their genetic code, and scientists already can modify it.

Many see the possibility of defeating many serious diseases, including cancer, in genetics. Today, there are promising gene therapies against cancer – they allow us to edit DNA information. This enables specialists to "remove" harmful genes and activate useful ones.

FUN FACT

THE WORLD'S FIRST HUMAN-APE HYBRID

In 2019, an international team of scientists from China, the United States, and Spain, led by Spanish biologist Juan Carlos Izpisua, created the world's first chimera ape embryo with human cells. The experiment was conducted in China because there are allowed experiments with gene modification, but due to ethical qualms, the embryo was given only 14 days to live.

Chimeras are animals or plants whose cells contain genetically distinct material. According to scientists, the creation of such organisms will help solve the transplantation issue, because human organs can be grown in them.

In 2014, scientists at the Massachusetts Institute of Technology discovered one of the mechanisms of genome editing, CRISPR/Cas9. This technology allows cutting double-stranded DNA anywhere, while other methods have their limitations and are more difficult to perform. With this method, it has become possible to perform faster and more precise modification of DNA in the genome, as well as to introduce more than one gene into a modifiable organism at a time. This method is cheaper and simpler than previous developments. Not surprisingly, CRISPR/Cas9 has been used more in recent years and is finding new applications.

Specialists are developing customized programs to significantly improve overall health: techniques such as genome analysis, gene therapy, and molecular diagnostics using biomarkers are already yielding positive results in animal experiments. And in 2021, the first human study of Alzheimer's disease gene therapy was launched: researchers from the University of California, San Diego injected patients with a harmless virus that can activate a gene associated with slowing and preventing the process of neurodegeneration.

FUN FACT

THE SECRET OF YOUTH LIES IN "JUMPING GENES"

The question of what biological mechanisms underlie eternal youth has been troubling scientists for decades. The answer, experts believe, may lie in the DNA of the long-lived insects – termites.

On average, termites live from two months to two years when it comes to workers and soldiers, but their queens live ten times longer (from 25 to 50 years). If termites lived as long as humans, monarchs would reach the age of 1,000 years.

A team of scientists led by Professor Judith Korb of the University of Freiburg found that aging in termites of Macrotermes bellicosus species is associated with the activity of mobile genetic elements, or "jumping genes" – self-copied DNA elements that can move independently and thereby disrupt the normal functioning of other genes nearby, leading ultimately to aging and death. In monarchs, jumping genes are inactive, so these insects are well protected from aging. However, scientists must find out how they managed to suppress this mechanism.

Many diseases are based on genetic disorders or genetic predisposition. By identifying the genes that cause a particular disease, we can start treatment or prevention in time. Recently, the polymerase chain reaction (PCR) method has been widely used, which allows to multiply of a DNA segment into billions of copies in a few hours. For PCR tests, we can use just one cell or a small sample of tissue. This is very important, for example, for early diagnosis of diseases: we can take one embryo cell obtained by fertilization in vitro, perform genetic screening and, if necessary, carry out the treatment of the unborn child. Over time, this can have a positive impact on the health of future generations by reducing the spread of disease.

Scientists are actively studying anti-aging methods and identifying the genes that control this process. For example, they compare the genome of old and young people and use a computer to identify where the most genetic damage occurs.

In addition, it is known that aging is caused by telomere shortening during cell division. Telomeres are located at the ends of chromosomes and they protect DNA. At the end of the XX century, it was discovered that the activation of telomerase, which is responsible for telomere lengthening, makes a single cell immortal. The anti-aging potential of telomerase has been discussed for many years.

Scientists have developed special injections of the telomerase gene, TERT. The specific approach of using TERT therapy was confirmed by molecular biologist Maria Blasco in mice, where she prolonged both the average survival and the maximum age of the animals²⁵. In one group, mice received TERT injections at 420 days of age, which increased median survival by 24 % and maximum life expectancy by 13 %. In another group, rodents received injections at 720 days of age, which helped increase median survival by 20 % and maximum life expectancy by 13 %.

The results suggest that gene therapy may not only conquer all genetic disorders but also help humanity to defeat aging and death in the future.

A WORD ON SEQUENCING

DNA and RNA discovery gave science a powerful impetus to find reliable ways to sequence nucleotides. They are all united by a generic term – sequencing.

Sequencing technologies bring us closer to the future of genomic medicine. The deciphering of the genetic code has opened unprecedented prospects for scientists and physicians and has made it possible to solve many applied and fundamental problems: the development of new medicines, vaccines, and other products. Sequencing technologies not only help identify deep-seated diseases, but also allow us to learn more about the evolutionary history of humans, animals, and plants, as well as understand the causes of mass extinctions on Earth. By sequencing the genomes of the remains, scientists learn about the origin of species, the body age, and habitat conditions. By studying DNA fragments, scientists identified a new species of ancient people, the Denisovans²⁶.

Initially, sequencing was a very expensive method and only very rich people and organizations could afford it. Today, almost every scientific or medical laboratory can order or perform this procedure independently. Many companies are performing genetic testing and offering individualized recommendations to help improve health and prolong life. If you know that one of the genes is defective, you can mitigate its harm in different ways, such as lifestyle adjustments or drug therapy. This personalized approach is more advanced than the current level of medical development and is undoubtedly useful for the aging research field.

Thus, by reading the genome, it is possible to unlock the secrets of longevity encoded in it and change human life for the better by activating the "immortality genes" and protecting them from damage.

WHAT IS A METAGENOME?

Sequencing technology has opened new horizons not only for geneticists but also for microbiologists. Previously, scientists could only study the genome of microorganisms that could be grown on a nutrient medium. Due to sequencing, it is now possible to obtain information about microbes with only their DNA, RNA, or even fragments of genetic material. The development of this technology led to the appearance of a new branch of molecular genetics – metagenomics.

In this discipline, experts do not study the genes of specific cells within a body or in microbial cells, but rather the metagenome – the set of all the genes in any given sample.

Samples for subsequent metagenomic analysis can be obtained from different areas of the human body: oral, intestinal, and vagina metagenome. It can also be samples obtained from the environment. For example, in 2003, scientists used the sequencing method for metagenomic analysis of ocean water samples obtained from different parts of the planet²⁷. As a result, only in a sample from the Sargasso Sea, experts found about two thousand DNA samples of different species, including 148 bacteria previously unknown to science.

The study of the metagenome helps not just to perform a genetic analysis of microbes, but to understand the laws of microbial communities, and to define their mutual influences and metabolic chains. It allows us to get a better understanding of life in the microcosm inside us and around us.

CONCLUSION

Currently, DNA analysis forms the basis of biological research and is used in biotechnology, virology, and medical diagnostics. New technologies are being developed and improved to detect various diseases, such as diabetes, cancer, and neurodegenerative and cardiovascular diseases, which greatly reduce the quality of life and contribute to the overall mortality statistics of the population. Early diagnosis and precise treatment were made possible by genetic methods and a better understanding of the body's structure at the molecular level. They will lead to prolonged life and help defeat aging.

CHAPTER 3
EPIGENETICS

EPIGENETICS IS A RELATIVELY NEW BRANCH OF GENETICS WHICH IS CALLED ONE OF THE MOST IMPORTANT DISCOVERIES SINCE THE DNA WAS DECODED, AS IT PROMISES TO TURN OUR LIVES AROUND AS WELL AS THE LIVES OF OUR DESCENDANTS. PREVIOUSLY, IT WAS THOUGHT THAT THE GENETIC CODE WITH WHICH WE ARE BORN DETERMINES OUR ENTIRE EXISTENCE. BUT NOW IT IS KNOWN THAT WE CAN CONTROL GENES: "TURN ON" OR "TURN OFF" THEM BY VARIOUS FACTORS, SUCH AS LIFESTYLE OR THE ENVIRONMENT. THIS MEANS THAT GENETICS DOES NOT PREDETERMINE OUR HEALTH STATUS OR LIFE EXPECTANCY – WE "PUSH THE BUTTONS" OF GENETIC CHANGES AND THEREBY CONTROL OUR FUTURE DESTINY.

"OVER" GENETICS

Epigenetics (the Greek prefix epi means "over," or "above") is the study of stable phenotypic changes that do not involve alterations in the DNA sequence. In simple terms, it studies how genes are "turned on" or "turned off" by environmental factors. You can imagine how a certain "commander" orders the genes to work or to rest ("stay silent") at a certain moment, depending on the signal received. This "commander," who determines the activity of genes, is an epigene. Ecological environment, diet, physical activity, bad and good habits, toxins, viruses, biochemical processes in the body, as well as thoughts, emotions, feelings, and human behavior are signals to it.

DNA is the code that an organism uses to build and rebuild itself. But the genes also need "instructions" to structure the course of work. And the collection of such "instructions" is our other code, the epigenetic program, which tells the body how our genes shall work.

HOW THE EPIGENETIC MECHANISM WORKS

The main ways to control gene activity are histone modification and methylation. Histones are special proteins to which the DNA in the cell nucleus is wound around, like a coil, to form a tight pack, the nucleosome. The tighter this pack, the less DNA is available to the enzymes that conduct transcription – synthesis of RNA from the DNA matrix. And since there is less RNA, less protein is produced. This means that the gene in this area will have little or no activity. However, signals from the external environment can contribute to a looser arrangement of these "coils," so that enzymes gain access to this DNA section. This means that RNA, and then proteins, can be synthesized – the gene is active.

The second mode of gene regulation is methylation, i.e., the addition of a methyl group – CH3 – to DNA. As a result, cytosine is transformed into 5-methylcytosine. Once the signal is received, the methyl group attaches to the DNA, which prevents enzymes from binding to it and changes the density of the nucleosome, as with histone modification, making genes inactive. In contrast, the process opposite to methylation, i.e., demethylation, activates previously "silenced" genes, which promotes the formation of new proteins.

Understanding the mechanisms that "turn on" and "turn off" genes can give science and medicine the ability to regulate the aging process, as well as to control and treat various diseases, including those of genetic origin. For example, "uncontrollable" genes are often "guilty" in the development of cancer – their "silencing" will stop further growth of the tumor. Therefore, the most prestigious scientific prizes are awarded for research in this field: for example, in 2006, American scientists Andrew Fire and Craig Mello were awarded the Nobel Prize for the discovery of another epigenetic mechanism – RNA interference.

FUN FACT

ONLY 5-10 % OF DISEASE DEVELOPMENT DEPENDS ON GENETICS

Canadian scientists at the University of Alberta conducted the largest meta-analysis, summarizing data from 569 genetic studies over two decades, and concluded that the association between most human diseases and genetics is very low – only 5-10 %. This means that human life and health are not predetermined by genes, but depend more on lifestyle and environment.

In their work, the researchers studied the relationship between gene mutations known as single-nucleotide polymorphism (SNPs) and various diseases and conditions. Many SNPs are considered risk factors for the development of hundreds of diseases, but the results of a meta-analysis have shown that this relationship is highly questionable.

Experts have found that most diseases, including many cancers, diabetes mellitus type II, and Alzheimer's disease, are only 5-10 % or less dependent on genetic factors. However, there are exceptions: for example, Crohn's disease, gluten-sensitive enteropathy, and age-related macular degeneration, for which the genetic risk is 40–50 %.

Despite these rare exceptions, it has become apparent that in most cases the development of disease is related to metabolic disorders, environmental and lifestyle factors, or exposure to dangerous bacteria, viruses, and toxic substances. It can be concluded that we should not blame deviations in health on heredity, and it is better to monitor the ecological security in which people live and work: food, water, air quality, etc., as well as lead a healthy lifestyle.

We can monitor epigenetics in action through the observation of the lives of identical twins who have identical DNA at birth. These observations show how strong the differences in gene expression of twins can be if they live in different conditions and lead different lifestyles. In theory, the disease in twins should develop equally, but it is far from being true: depending on various factors, only one of them may have symptoms.

This finding supports a study conducted in 2005²⁸. Scientists studied several dozen pairs of identical twins 3–74 years old. It turned out that people did have similar gene expression in childhood because they were in about the same conditions: they lived in the same house, went to the same school, and ate similar food. However, the older the twins got, the more differences there were between them. And when the siblings separated as adults, and started to lead different lifestyles, to have some different hobbies, to work in different fields, the number of these differences increased several times.

It is the same with ordinary people: as soon as you change your lifestyle in one way or another, your genes will manifest themselves differently. And this changed methylation profile we pass on to our children! Why don't we then take advantage of this ability to make genes work for better health, slower aging, and longer life? Knowing how the epigenetic mechanism works can enable you to control your genetic code and thereby silence the "bad" genes inherited and activate the "good" ones. So how do we start the chain of beneficial epigenetic changes?

FACTORS THAT MAY AFFECT OUR GENES

Although epigenetics is still in its infancy, much is already known about the ways to change the activity of hundreds or even thousands of genes.

NUTRITION. In 2003, a study at Duke University (USA) showed that nutrition not only changes DNA operation but also causes hereditary transformations²⁹. Test objects were so-called agouti mice. They differ from normal mice in the more active special gene responsible for the formation of the agouti signal peptide. This protein makes animals prone to obesity, increases the likelihood of tumor development, and produces a pigment in the follicles, giving the fur a yellow color (instead of brown or black).

In the study, female agouti mice shortly before mating were "put" on a special diet rich in folic acid, vitamin B12, and the amino acids, choline, and methionine. This dietary pattern was maintained throughout pregnancy and the lactation period. Most of the young mice were born with normal color and healthy metabolic processes, with no tendency to become obese as adults. Moreover, several more generations of rodents born from the first offspring of agouti mice also showed no signs of agouti peptide activity, although they adhered to a standard diet.

Such results, experts say, are very applicable to humans as well. They state that folic acid and vitamin B12 deficiency in pregnant women leads to negative changes in methylation, which can lead to pathologies manifesting not only in the child but even in their future children and grandchildren.

A correct diet and healthy lifestyle can help silence the expression of hundreds of genes associated with cancer development. This was shown in a 2008 experiment carried out by scientists from the University of California, San Francisco³⁰. For three months, men diagnosed with prostate cancer were on a low-fat plant-based diet and received vitamin and amino acid supplements. In addition, an exercise program was designed for them. As a result, patients were able to change the expression of more than 500 genes: activate 48 genes reducing tumor growth and suppress 453 genes associated with tumor overgrowth.

SPORT. Exercise at least twice a week can change the activity of several thousand genes. A study conducted by researchers from Lund University (Sweden) showed that in volunteers who regularly attended aerobic training for six months, there were epigenetic modifications in 7,663 genes associated with delayed development of type II diabetes and obesity³¹.

Exercise can slow down the development of obesity, even in those who have a genetic predisposition. An international team of experts studied data from more than 200,000 patients and concluded that regular exercise suppresses the activity of 11 genes associated with weight gain³². Among them is the FTO gene, which increases the likelihood of obesity by 30 %.

Experts from Massachusetts General Hospital proved that increasing physical activity can reduce the risk of depression among people who are predisposed to this disorder³³. They calculated the genetic risk for each of the eight thousand participants in the study and then surveyed how long it took them to exercise and what sports they did. Then they monitored the health of the subjects for two years.

The most active people showed a lower tendency to develop depression, even though they had a high genetic risk. The likelihood of a new episode of depression for them was reduced by 17 %.

According to scientists, four hours a week would be enough to change the expression of the right genes and protect against repeated episodes of depression. It does not matter what kind of physical activity you do: both high-intensity exercises (aerobics, machines, dancing) and moderate-intensity ones (yoga or Pilates) are good.

BAD HABITS. Tobacco smoking is one of the most powerful negative lifestyle factors that affect not only the whole body but also gene activity, "turning on" and "turning off" entire clusters of different genes. Epigenetic modifications can cause the development of many diseases: cancer, chronic obstructive lung disease, cardiovascular disease, osteoporosis, etc.

Every year more studies are proving that smoking irreparably changes the epigenetic state of human DNA. An international team of experts analyzed and compared the DNA methylation profiles of former and current smokers, as well as those who have never smoked³⁴. The researchers came to the following conclusions.

● Smoking changes the activity of more than seven thousand genes – i.e., more than a third of all known protein-coding genes that make up our genome.

● In people who quit the bad habit, only five years after quitting, most DNA methylation sites returned to the levels seen in those who never smoked.

● However, there were also areas of DNA that remained with the "nicotine" tag even 30 years after quitting smoking and continued to function in the same way as active smokers.

● Most of the genes with altered expression due to smoking have been associated with numerous diseases, such as cancer and heart disease.

As for alcoholism, experts from Cambridge University (UK) proved that alcohol abuse causes irreversible changes in the DNA structure of blood stem cells (double-strand break, poor DNA repair – the function of damage repair, rearrangement inside chromosome parts), which leads to malignant tumors³⁵. For example, alcohol dependence increases the risk of developing at least seven types of cancer, including the most common, breast, and colon cancer.

Numerous studies have shown that drugs, both light and heavy, are not only harmful to those who use them but also contribute to birth defects and genetic diseases in their children.

American researchers at Duke University have found a potential link between cannabis use by fathers and the development of mental illness in their children³⁶. In men who used marijuana, they found several adverse changes in gene activity associated with autism, schizophrenia, and post-traumatic stress disorder. Experiments on rats showed that the born offspring had similar epigenetic changes. This confirms the likelihood of the "marijuana" tag transmission for generations. Another study by the university showed that the father's use of marijuana affects the child's cognitive functions: abnormalities were found in certain brain areas related to learning, memory, reward, and mood³⁷.

ENVIRONMENT. One of the factors that certainly affects gene expression, and thus our well-being, is air quality. Experts from Monash University in Australia proved that even short-term exposure to polluted air adversely affects the activity of six genes responsible for the severity of oxidative stress and inflammatory reactions in the body³⁸. The "abnormal" methylation profile that was found in these DNA regions was associated with the development of dangerous cardiovascular, respiratory, and cancer diseases, as well as an increased risk of premature death.

CONTACT WITH PESTICIDES. Many recent studies have examined the effects of chemicals on gene expression, and several toxins have been identified that leave epigenetic tags in DNA. These are bisphenols in plastics and epoxy resins, phthalates in vinyl floors, plastic, perfluorochemicals used to create non-stick coatings on cookware, pesticides, herbicides, salts of heavy metals, etc. Russian scientists from the Institute of Experimental Medicine of the RAS conducted an experiment, the results of which showed that the introduction of a single dose of bisphenol into a pregnant female mouse disrupts the methylation profile of several DNA regions, which causes problems in fetal development³⁹.

Significant epigenetic modifications can be caused by vinclozolin. This was proved by American scientists from the University of Nebraska-Lincoln and Rutgers University (USA) and showed another good example of epigenetic imprinting⁴⁰. In the experiment, pregnant rats were given vinclozolin in their food and observed how it would affect their babies. It turned out that male children had problems with sperm quality and quantity as they got older. And this effect persisted for four generations of laboratory animals and then disappeared.

STRESS, RELATIONSHIPS, THOUGHTS. Not only "clear" signals, such as food or toxin exposure, can change gene expression. Even the way a person thinks and feels affects gene activity. Genes very quickly respond to prolonged stress, constant anxiety, fear, arguments, and anger. They start a chain of adverse biochemical processes in the body, leading to disease development. But it is important that our genes also respond with a positive "reaction" to showing gratitude, love, and optimism.

A team of experts from Ohio State University (USA) conducted a study to find out how an ordinary family argument can affect the rate of wound healing, an important indicator of genetic activity⁴¹. Scientists gave slight injuries on the skin of all participants and monitored the rate of healing by the levels of three proteins responsible for tissue regeneration. During the first visit, the couples had to talk about any pleasant topic, and during the second visit, they had to remember their last unresolved argument. It turned out that after a family quarrel, spouses' wounds healed more slowly and the levels of produced proteins responsible for healing were lower than after a pleasant conversation. And in the most hostile couples – those who argued with mutual recriminations, humiliations, and accusations – the injuries took even longer to heal than in partners who were less hostile to each other. With thoughts and emotions alone, the spouses were able to induce appropriate epigenetic changes.

CONCLUSION

Discoveries in the field of epigenetics, which increase every year, convince us that genes are not a sentence: it does not matter whether we inherit "good" or "bad" genes, it is important how we use them. Most people probably have the potential for active long life in their genes. And in the future, no doubt, we will find a way to unlock it.

CHAPTER 4
BODY

IF YOU WANT TO PROPERLY USE SUCH A COMPLEX MECHANISM AS THE HUMAN BODY, IT IS NECESSARY TO UNDERSTAND HOW IT IS BUILT. A HUMAN IS VULNERABLE TO DISEASE WITHOUT KNOWING THEIR PHYSIOLOGY. THE MAIN TASK OF THOSE WHO WANT TO BE HEALTHY AND LIVE LONGER IS TO SUPPORT THE WORK OF THE BODY.

WHAT OUR BODY IS

CELLS

The human body is made up of cells, the basic structural units, which work together and perform the various functions necessary to sustain life.

The human body weighing 70 kilograms consists of an average of 30 trillion cells. And most of them are erythrocytes – they account for 84 %. Then there are thrombocytes – 4.9 %, bone marrow cells – 2.5 %, vascular endothelial cells – 2.1 %, lymphocytes – 1.6 %, and hepatocytes – 0.8 %. Muscle and fat cells account for 0.1 % of the total cell number⁴².

For the body to function properly, there is a continuous process of replacing old cells with new ones. About 3.8 million cells are renewed every second, and almost 330 billion cells per day. Even when a human dies, it will be a while before all the cells in the body die.

Researchers at the Karolinska Institute (Sweden), led by biologist Jonas Friesen, calculated the lifespan of individual cells, finding that they change differently – depending on the type⁴³. For example, the epidermal cells that make up human skin are renewed every two weeks. Erythrocytes, which carry oxygen from the lungs to the tissues of the body, live for four months, while neutrophils, a type of white blood cell, live only for two days.

The life of liver cells is between 300 and 500 days. The epithelial cells lining the intestine last only five days and then are replaced by new cells – they are among the shortest-lived in the body. Without them, the average age of all intestinal cells is 15.9 years. Skeletal tissue cells live about 10 years, while cells of rib muscles live 15.1 years⁴⁴.

But not all cells are renewed: for example, the cells of the retina and lens do not change throughout life. This explains the natural deterioration of vision with age. For a long time, it was believed that nerve cells also live as long as humans, die with aging, and do not renew. However, recent data have shown that new neurons are formed from stem cells, but it is not yet known how functionally full-fledged they can be. Scientists estimate that the adult male brain contains 86.1 ± 8.1 billion neurons⁴⁵.

According to Friesen, the average lifespan of a human cell is 7–10 years. This statement has caused the popular misconception that "the human body renews every seven years." This is not true, because cell replacement is a continuous process: the body renews in different parts at different rates depending on the needs and functions.

ATOMS

At a more fundamental level, cells consist of molecules, which, in turn, consist of atoms (from Greek ἄτομος "uncuttable"). An adult human body weighing 70 kg contains about 6.7 octillion (6.7 × 10²⁷) atoms, 96.5 % of which are chemical elements⁴⁶ such as hydrogen, oxygen, carbon, and nitrogen. About 4 % are other ones: calcium, phosphorus, sodium, potassium, sulfur, etc.⁴⁷.

Most of the chemical elements come from the environment. When we eat, drink, or breathe, atoms enter the body. They not only compose cellular structure but also ensure the flow of chemical processes, supporting vital activity.

When we exhale, sweat, or lose body tissues, i.e., excrete anything into the environment, the atoms return to the Earth's biosphere. From there they enter the bodies of other people, animals, and plants. Thus, most of the atoms in the body are constantly replaced. And they do it differently – some in a few hours, others in a few years.

All these atoms are not regenerated every day. They have been around for billions of years and existed long before the Earth was formed. The first atoms formed in the early days of the universe, 13.7 billion years ago, about 380,000 years after the Big Bang. By that time, the universe had already cooled enough for electrons and protons to combine and form hydrogen and helium. The first stars were born from these atoms, and because of nuclear reactions in them, other heavier elements were formed.

Every particle of our body was once inside such stars or was formed because of its death. "Every atom in your body came from a star that exploded. It is the most poetic thing I know about physics. And, the atoms in your left hand probably came from a different star than your right hand. You are all stardust," writes physicist Lawrence Krauss in his book "A Universe from Nothing."

BODY SYSTEMS

Cells composed of atoms form tissues: epithelial, connective, muscular, and nervous. And tissues form organs. The latter, in turn, are combined into systems.

All systems interact closely with each other. For example, the digestive system provides the intake of nutrients in the blood for energy. However, the cells can produce energy only with oxygen, which is supplied by the respiratory system.

HOMEOSTASIS

Each cell can only function under certain conditions: temperature, acidity level (pH), a certain concentration of fluids, electrolytes, and oxygen – there are a lot of factors. Maintaining the balance of the body's systems necessary to sustain life is called homeostasis.

Under the influence of harmful factors which can damage the body, there is a redistribution of innate resources: with hypothermia, the body provides a flow of extra blood and, consequently, heat to the vital organs by narrowing the blood vessels of the skin. When overheated, on the contrary, skin vessels expand, which increases heat loss and remains constant internal temperature.

A well-established system of self-regulation is the most crucial component for a long and healthy life. The functioning of the body allows it to respond adequately to dangers and adapt to changing environmental conditions. Dysfunction in one organ inevitably affects the functioning of other organs and systems. For this reason, in old age people often face several diseases at once, each of which provokes and accelerates the progression of other disorders. A complication of diabetes mellitus, which is often associated with obesity, is a vascular disruption in the whole body, which in turn increases the risk of cardiovascular disease. Joint problems limit a person's mobility, which contributes to weight gain, which, in turn, puts stress on the joints. It is a developmental factor of a wide range of diseases.

It is very important to bear in mind that even a small health issue may result in a cascade of abnormal changes that lead to serious diseases. Even a small nidus of persistent infection, such as a decayed tooth or chronic tonsillitis, provokes the development of inflammation in the digestive tract and creates determinants for intestinal issues. Any violation in the supply of macro and micronutrients will affect every body's cell function with time.

Both physical and mental aspects are important for keeping a healthy body. It is known that chronic stress is an equally important contributor to disease than, for example, nutritional disorder, physical inactivity, or bad habits. On the background of distress, the level of cortisol – a hormone of chronic stress – increases, which negatively affects the immune system, provokes obesity and increases the risk of depression.

Thus, to maintain the stability of the internal environment, and to ensure its functional integrity, it is necessary to take care of all aspects of health. This is achieved by daily measures to prevent both physical and mental disorders, primarily by following a healthy lifestyle, as well as by responding quickly and appropriately to any abnormalities in health.

BRAIN – BODY, BODY – BRAIN

The brain controls the body like a powerful computer. It stores and constantly updates information. Since the brain contains a unique "body map," it can monitor the condition of internal organs and regulate important life processes – heart rate, respiration, blood pressure, sleep quality, digestion, and others.

However, this connection is not one-way. The brain receives information about the work of any organ due to receptors – nerve endings that transform stimuli of

the external and internal environment into electrochemical impulses. These impulses are sent through the spinal tracts to the brain, which, based on the information received, regulates the work of peripheral organs.

Due to the connection between the body and the brain, the organs are sensitive to changing body needs. A water deficit signal in the body turns into thirst because of vasopressin. This hormone, responsible for fluid maintenance, affects both the brain and the kidneys, causing them to inhibit fluid excretion.

EXERCISE TO BE HEALTHY

In the modern world, it is important to monitor the condition of your body. It is easy to yield to laziness, stress, and bad habits and not think about what affects the quality of function of organs and the body as a whole. Lifestyle determines human health: junk food leads to weight gain and the development of chronic diseases – obesity, osteoporosis, type 2 diabetes, and others, and with low physical activity the human also deprives themselves of several advantages. In addition, psychic tension, low or high sleep hours, bad habits, etc. affect the overall health. Many aspects and everyday decisions determine how well the body will work not only now, but also in the future. What is the first thing you need to pay attention to maintain, strengthen and improve the health of your own body?

Experts urge monitoring the diet. It should be balanced, diverse and contain as few harmful substances as possible. You need to introduce into the diet as much as possible vegetables and fruits, which contain vitamins and minerals. Eating a healthful diet will help reduce the number of pathogenic microorganisms in the intestine and increase the number of beneficial bacteria that help digest food. Besides, it is important not to forget to drink enough water to avoid dehydration, which in turn leads to fatigue, lapse of concentration, mood swings, and even urinary tract infections.

FUN FACT

THE ABILITY TO HEAR YOUR BODY CREATES A POSITIVE BODY IMAGE

Scientists from Anglia Ruskin University (UK) believe that awareness of how the body functions and attention to feelings allow you to better perceive your own body. Therefore, a human who perceives their body positively better reads and correctly interprets its signals, such as hunger or a sense of fullness. The study involved about 200 people, residents of Great Britain and Malaysia. After a preliminary fast, volunteers were asked to drink water and talk about their feelings. Participants also answered questions regarding their body perception and understanding of how it works.

It was found that people with a positive body image, aware of the principles of its work, experienced more intense feelings from drinking water on an empty stomach, compared to participants with a negative image of themselves and a worse understanding of physiology.

Experts explain that body image refers to thoughts and feelings related to appearance, and positive body image refers to actions based on love for the body, attention, respect, and correct interpretation of its signals. According to scientists, the better human treats and takes care of the body, the better they understand its "language." In turn, increased attention to the signals coming from, for example, the stomach and intestines, allows us to better imagine the processes, to assess the body function higher, and to form a positive body image.

"Our study shows that there is a direct connection between bodily awareness – in this case, the feeling of fullness – and body image," explains lead author Jennifer Todd. "In other words, people who are more aware of body functions, give their bodies a higher rating."

Experts emphasize that the inability to correctly decode internal signals, such as feelings of fullness or hunger, contributes to a negative body image because of an over-reliance on external characteristics related to appearance (e.g., shape and size).

An active lifestyle improves not only the cardiovascular and musculoskeletal system, but also provides protection against many diseases, rejuvenates the body, and prolongs life. Well-chosen workouts improve mood, sleep quality, and blood circulation, and reduce high blood pressure and the risk of heart disease. And even here, variety is great: you can walk, jog, dance, do aerobics, and ride a bike. You must realize that life only happens in motion, so you must move as much as possible.

It is important to know that even the way a human breathes affects their health. Improper breathing is dangerous, because less oxygen enters the lungs, which means that the functions of other organs can be impaired due to oxygen imbalance. The skin condition depends on the lungs: there is a high risk of wrinkles with a violation of gas exchange.

You need to quit bad habits: any addiction leads to physiological and psychological problems. Smoking increases the risk of premature death by 40 %, and smoking one pack a day by as much as 400 %. You should limit your alcohol intake, as excessive consumption of alcohol increases the risk of cancer, heart disease, cirrhosis, and others.

Body health depends firstly on lifestyle. Therefore, it is the human who is fully responsible for the condition of their body. Keeping the body in shape helps to prevent the development of many diseases, improve overall health, maintain it, and high activity for years to come.

CHAPTER 5
BRAIN AND NERVOUS SYSTEM

"THE WORLD IS SMALL, BUT THE HUMAN BRAIN IS IMMENSE," WROTE THE GREAT GERMAN ROMANTICIST FRIEDRICH SCHILLER IN HIS DRAMA "WALLENSTEIN'S DEATH." "ENGIST DIE WELT, UND DAS GEHIRNISTWEIT" TRANSLATES FROM GERMAN AS "THE WORLD IS NARROW, THE BRAIN IS WIDE." IN TERMS OF LOGIC, IT MAY SEEM ABSURD, SINCE IT IS THE WORLD THAT CAN BE CHARACTERIZED AS "WIDE" AND "IMMENSE," WHILE THE PHYSICAL PARAMETERS OF THE HUMAN BRAIN ARE EASILY MEASURABLE.

Yet we realize that we are talking not just about the organ enclosed in the braincase, but about what it generates: mind, consciousness, something truly immeasurable and spanless, which makes us human.

Brain damage – trauma, tumors, age-related changes – often has severe and sometimes irreversible consequences. And it is not just because the brain has vital centers, controlling something like breathing and heartbeat. Adverse changes in the structures responsible for higher nervous activity often lead to personal degradation and anomie. Loss of memory, cognitive powers, and full communication "turn off" the person from society, leaving them to a helpless existence. That is why maintaining brain health, preventing age-related disorders, and slowing their progression is a priorities for people who intend to live happily ever after.

HOW DOES HUMAN NERVOUS SYSTEM WORK?

The human nervous system consists of central (CNS) and peripheral (PNS) systems. The CNS consists of the brain and spinal cord, and the PNS consists of nerves "supervising" the work of each cell in the body. The main task of the nervous system is to combine the work of all body organs, tissues, and cells into a harmonious "mechanism," as well as to provide a rapid and adequate reaction to changes in the internal and external environment. The nervous system works in close tandem with the endocrine (hormonal) system, forming a neuroendocrine system that regulates the entire body with nerve impulses and special chemical matters – hormones.

BRAIN

The brain is the supreme commander of the nervous system, controlling the entire body. In addition, its unique structure of it is the basis for the higher mental functions that underlie consciousness. The brain weighs only 1.2–1.4 kg, representing an average of about 2 % of the human body weight. The male brain generally is 10–12 % heavier and 10 % bulkier than the female brain⁴⁸.

The brain consists of several divisions.

● The largest part of the human brain is the forebrain. The cerebral cortex is a part of it. Both hemispheres (right and left) are divided into four lobes: frontal, occipital, temporal, and parietal. The cerebral cortex is responsible for the perception of all information coming from the external and internal environment: visual, auditory, olfactory, gustatory, and somesthetic cortices are located here. The cortex is also responsible for the human higher nervous activity, including thinking and speech.

● The midbrain contains the visual and auditory centers, which are responsible for processing impulses from the corresponding analyzers. In addition, the midbrain has a tremendous impact on the cerebral cortex. If the cortex is the "consciousness realm," then the midbrain is the "kingdom of the subconscious." The processes occurring in the midbrain can stimulate or inhibit the processes occurring in the cortex. There is also dopamine, a neurotransmitter that plays a key role in the formation of motivation, healthy habits, and addiction, is synthesized.

● The diencephalon mediates the transfer of stimuli to the hemispheres and helps adapt adequately to environmental modifications. Regulates the work of metabolic processes and endocrine glands. Manages the cardiovascular and digestive systems. Regulates sleep and wake, water, and food intake.

● The cerebellum is a brain region that is primarily responsible for maintaining balance and load distribution between muscles, unconscious body skills, and bodily memory.

● The medulla oblongata is an extension of the spinal cord. Nerve pathways that carry information from the whole body and back pass through it, as well as breathing and blood flow control centers. Damage to the medulla oblongata leads to quick death. It is connected to the overlying parts of the brain by the pons, part of the brain stem.

NERVE CELLS

The main structural unit of the central nervous system is the nerve cell or neuron. Neurons consist of a body and several projections. Nerve cell bodies form the gray matter of the brain and spinal cord, and the long myelin-covered projections form the white matter. Gray matter forms the cerebral cortex and the underlying nuclei, and the white matter forms the nerve pathways – a kind of "wires" through which different parts of the brain and other structures "communicate."

At last count, the number of neurons in the cerebral cortex is 14–16 billion, while in the cerebellum is 55–70 billion⁴⁹.

The neuron body contains many fibers that form the cytoskeleton: it helps the nerve cell to keep its shape. It also forms some sort of "tracks" where vesicles with neurotransmitters are delivered to the ends of the projections. There are two types of projections – short (dendrites) and long (axons). Most often, neurons have many dendrites and only one axon.

Axons can transmit nerve impulses over long distances – to other brain structures, to the spinal cord and to target organs. As a rule, several neurons located above or below the "author" of the impulse are involved in impulse delivery from the brain to the "distant regions" and back.

Axon terminals approach the body of the next chain member, releasing a neurotransmitter into the gap between the terminal and the body (or projection) of the other neuron. These "meeting places" are called synapses⁵⁰: this is where the electrical impulse is converted into a chemical. The next neuron "receives" the chemical signal and converts it again into an electrical one, sending an impulse to its destination.

Sometimes there are several such "stop-overs" on the way of "agents" to the destination – this system makes it possible to maintain a high intensity of the impulse, not allowing it to fade away. Axons are covered with myelin sheath, which is like an electrical insulator. Myelin consists of glial cells, as will be discussed later. Short projections of neurons – dendrites – help to set "local communication" between neurons. They are myelin-free. Each neuron is connected to thousands and tens of thousands of other neurons and target cells with short and long projections.

NEUROGLIA: THE BRAIN'S LIFE SUPPORT AND DEFENSE SYSTEM

Besides neurons, the "base" cells of the brain, the nervous system includes auxiliary structures – glial cells. There are several types of glial cells: for example, astrocytes, oligodendrocytes, microglia, and microglia. For many years the number of glial cells was believed to be exceeding the number of neurons by 8–10 times, but nowadays, it is proved that the ratio of neurons and glial cells is approximately the same⁵¹.

Glial cells are involved in the formation of the blood-brain barrier, a filter protecting the brain from microbes, some cells, and toxins. Glial cells also form the microenvironment around neurons, transport nutrients to nerve cells, excrete waste, form myelin sheaths, etc.

FUN FACT

HOW THE "INTESTINAL BRAIN" AFFECTS THE ENTIRE BODY

The human intestine contains a unique cluster of nerve cells – the enteric nervous system (ENS). Sometimes it is also called the intestinal or "abdominal" brain. The ENS uniqueness, its difference from the nerve clusters in other organs, is associated with several characteristics. Firstly, it includes about half a billion neurons! Secondly, the ENS is very similar in structure to the brain. Several types of neurons can receive and send signals and provide the motor function of muscles. The enteric nervous system has its glial cells, which, as in the brain, nourish neurons and activate immune mechanisms. Thirdly, a huge number of neurotransmitters are synthesized in the intestine. The spectrum of the internal neurotransmitters in the ENS is as wide as in the central nervous system. Over 90 % of serotonin and 50 % of dopamine are synthesized in the body being produced in the intestine. Almost all ENS neurotransmitters are of bacterial origin.

All these factors underlie the fourth key feature of the ENS: its autonomy. Unlike other parts of the nervous system, the intestinal brain can function without control by the central and peripheral nervous system, even with extensive brain injury. At the same time, the brain, and the intestine nervous system are closely linked, forming the "gut-brain" axis⁵². Therefore, the ENS not only regulates the digestive tract but also affects the entire body.

Studies show that some diseases affecting the brain, such as Parkinson's disease, are associated with certain changes in the intestinal microbiota.

Scientists at Washington University reviewed 150 studies and found that age-related loss of glial cells (pericytes), which form the blood-brain barrier, significantly increases the risk of developing Alzheimer's disease⁵³.

Glial cells in the blood-brain barrier act as "pumps" that remove toxic beta-amyloid proteins from the brain. Clusters of these proteins are one of the causes of Alzheimer's disease. Disruption of the "pump," caused by age-related loss of glial cells, increases the risk of dementia. Scientists believe that due to a decrease of glial cells in the blood-brain barrier during aging, the brain starts, figuratively speaking, to "leak out," which contributes to cognitive impairment.

SPINAL CORD

The spinal cord is part of the human central nervous system and an extension of the brain. It is in the spinal canal and has the form of a long rod, which extends from the medulla oblongata. The rod center contains a spinal canal filled with cerebrospinal fluid. The central part of the spinal cord is represented by gray matter formed by the bodies of neurons, around which there is white matter formed by the long neuron processes.

White matter consists of nerve pathways through which impulses travel from the brain to the spinal cord (descending tract) and back (ascending tract). That is how different parts of the spinal cord come into contact. Gray matter contains sensory and motor neurons. Their projections connect and form sensory and motor roots, which also connect and form spinal nerves.

The spinal cord performs a conductive function – it is a link between the brain and the peripheral nervous system. At the same time, the spinal cord regulates some processes independently, without the direct involvement of the brain. For example, when we touch a heating object, we pull our hand back automatically. This reflex is formed at the spinal cord level – the movement occurs unconsciously.

NERVES (PERIPHERAL NERVOUS SYSTEM)

A total of 31 pairs of spinal nerves depart from the spinal cord – at the level of each vertebra. All spinal nerves contain sensory fibers, neuron projections that collect information from tactile, pain, temperature receptors of the skin, etc., and send it for "processing" to the central nervous system. They also contain motor fibers through which impulses from the brain and spinal cord travel to the muscles, making them contract.

As they move away from the spinal cord, the roots begin to branch, forming nerve trunks, large nerves, and then dividing into smaller ones. Each nerve ends with a nerve ending near a specific body part. All nerves divide into motor, sensory, and mixed (containing both types of projections) ones.

A separate group consists of 12 pairs of cranial nerves. The bodies of neurons, which projections form the cranial nerves, are part of the special clusters of gray matter, the nuclei of the brain stem. They go beyond the periphery from openings in the skull, and the areas they "work with" do not extend beyond the head and neck. The only exception is the vagus nerve, which plays a crucial role in regulating the work of internal organs.

The peripheral nervous system is divided into autonomic and somatic. The somatic nervous system regulates the functioning of the skeletal muscles, which are responsible for movements that we consciously control. The autonomic nervous system regulates the living environment, which is beyond our consciousness. These include breathing, heartbeat, sweating, etc.

For example, when we face any danger, the autonomic nervous system first activates: the pulse and breath quicken, cold sweat appears, and the muscles turn rigid. All these reactions are unconscious. And then the somatic nervous system comes into play: we decide "fight or flight" by giving the appropriate orders to our skeletal muscles.

In turn, the autonomic nervous system is divided into sympathetic and parasympathetic. The sympathetic nervous system is responsible for processes occurring in the waking state. The sympathetic nervous system manages the mechanisms allowing the body to maintain a tone and respond quickly to stressful situations. The parasympathetic system, on the contrary, regulates the processes occurring during rest and sleep: the heart rate slows down, breathing becomes rare, and vessels expand, but digestion, on the contrary, occurs more intensively.

Thus, the nervous system is a complex structure with multilevel regulation, which is carried out at both conscious and unconscious levels. Understanding the principles of the structure and functioning of the nervous system, and knowledge of buttons that we can push through our thoughts, actions, and lifestyle, are essential to preserving health and increasing life expectancy. Before you learn to "negotiate" with your nervous system, you need to understand the "language spoken" by neurons. Such "language" is a special molecule called a neurotransmitter.

HOW MEMORY FORMS AND HOW NOT TO LOSE IT WITH AGE?

Our memory is a unique storage of all the events and feelings in our lives, knowledge gained through spontaneous and focused learning, skills, and experiences. Memory is what makes us who we are, and shapes our personality. Therefore, impairment in the ability to store new memories, which is often seen in old age, reduces the quality of life.

However, the real tragedy is the process of memory degradation, the loss of an entire bunch of memories. This devastating phenomenon is specific to so-called neurodegenerative diseases, the most common of which are Alzheimer's disease and vascular dementia.

To see how to prevent these tragic age-related changes, it is important to understand what memory is, how and where it is formed, and what types of memory there are.

From a neurophysiological perspective, memory is a property of the nervous system that lies in the ability to store information about events in the world around, the body's reactions to these events, and the ability to "work" with this information: to reproduce it (recall) and change it, if necessary. A well-functioning memory is like a computer that stores all the downloaded files and opens them on demand. However, unlike a computer, our memories are not stored in folders – they are "written" in neural connections.

When we encounter new information (for example, when we begin to learn a foreign language) or new experiences (when we try to learn to drive a car), our nerve cells start to form new pathways in the brain with the help of projections and synapses. If we do not go back to that experience again, the connections disappear. Therefore, if a person starts to learn a foreign language, but soon quits, the next time they must learn again almost from scratch.

However, if information or action is referred to repeatedly, a hardly noticeable "path" in thickets of nerve endings gradually turns into a well-trod "road," and then into a high-speed "highway." And now we are, almost without thinking, speaking a new language, and driving on automatic. This indicates that "files" with the necessary information are firmly stored on our "computer."

SHORT TERM MEMORY

Some neural connections exist for a very short time: seconds and minutes, which is characteristic of short-term memory. Short-term memory allows the brain to work with small portions of information coming into it at the current time. Information can come both from external sources (what we see, hear, and feel at the moment) and from the depths of our memory – purposeful, or spontaneous recollection.

Areas in the frontal and parietal lobes of the brain, anterior cingulate cortex, and areas of basal ganglia are responsible for short-term memory.

The information storage time in short-term memory is usually no more than 20–30 seconds, in addition, it holds a very limited amount of information. According to various estimates, in a short time, a person can hold in memory from 4 to 7 objects. But there are also various techniques allowing to increase the number of memorized objects, for example, to group them by some principles or form associations. With constant repetition, "mental objects" move from short-term memory to long-term.

A form of short-term memory is working (operative) memory, allowing one to remember necessary information for just a few seconds. For example, enter the digits of a code sent by a bank to make a purchase, or type the phone number, dictated by a new friend, in the contact book. Working memory state is one of the most significant criteria used to assess a person's cognitive reserve. Its impairment is often observed with brain aging and can be considered one of the first signs of age-related dementia.

LONG TERM MEMORY

Unlike short-term memory, long-term memory is quite capable, both in terms of storage time (many memories can last until the end of life) and in terms of volume. In addition, many parts of the brain are involved in the formation of long-term memories. Long-term memory is divided into explicit and implicit.

Explicit memory allows one to consciously operate with information stored in memory, both personal experiences (episodic memory) and facts (semantic memory). The place where episodic explicit memory is stored is an area of the brain called the hippocampus. It keeps the information about, for example, going on vacation with your parents as a child and having coffee with a friend last week. Huge amounts of knowledge are stored in the cerebral cortex: here, for example, information concerning various facts, language, etc. is placed.

Amygdala is responsible for storing emotionally loaded information. Due to the neural connections in this structure, as well as the connections between the amygdala, hippocampus, and cerebral cortex, we can for many years remember situations in which we experienced a strong feeling of joy, shame, or fear. In addition, the amygdala plays a key role in the creation of new memories associated with fear. Therefore, the peculiarities of memory formation in the amygdala are actively studied by specialists involved in post-traumatic stress disorder, people who "run away" from the solution of life's tasks, because of the fear they once experienced, etc.

Implicit long-term memory is formed without consciousness: we can use it without a detailed recall process. The key brain structures responsible for storing implicit information are the basal ganglia and the cerebellum. Basal ganglia (or basal nuclei) are structures that are clusters of gray matter (nerve cell bodies) located deep in hemispheres between the frontal lobes and above the brain stem (on the border of the conscious and unconscious).

The basal nuclei store information about received rewards, and motor skills, so this structure plays a key role in the development of motor habits (piano playing, cycling, dancing, driving), that require less involvement of consciousness in the process of skills implementation as we learn. Lesion of the basal ganglia underlies the motor disorders in Parkinson's disease.

NEUROPLASTICITY

Studies show that as we use our brain, learn, and train our memory, it can change dramatically due to neuroplasticity.

Brain plasticity refers to the ability of the nervous system to change its structure and functions throughout life in response to environmental diversity. The study of neuroplasticity is particularly relevant when it comes to brain aging, recovery from injuries and strokes, and treatment of neurodegenerative diseases such as Alzheimer's and Parkinson's diseases.

Due to neuroplasticity, nerve cells can restore their structure and function, as well as form new synaptic connections. Neuroplasticity is based on two basic processes: the formation of new connections between nerve cells (synaptic plasticity) and the formation of new neurons (neurogenesis).

SYNAPTIC PLASTICITY

In childhood and adolescence, synaptic plasticity is a key property of the brain: the ability to form new connections between neurons helps to learn quickly, to perceive the world. A child's brain forms connections between neurons when encountering a wide variety of information and experiences. As you get older, the number of connections between neurons decreases. This process is called synaptic pruning. The older we get, the more selective our brain becomes in forming connections. It spends resources only on tracing neural pathways for the thoughts we come back to day after day.

Therefore, many adults' brains resemble a "cast" of every day worries. The neural impulses travel along pathways similar to an asphalt road. It takes enough effort and motivation to go off the beaten track and start to "tread" a new path in the neural thicket. At the same time, at any age, repetitive actions gradually lead to the formation of new neural connections.

NEUROGENESIS

It was long believed that the number of nerve cells remained unchanged throughout life: the claim that nerve cells do not regenerate was seen as an axiom. But in recent decades, the findings show that neurogenesis – the production of new neurons by neural stem cells (precursors of all body cells) – is observed in various parts of the brain even in old age.

Scientists from the University of Illinois, after studying postmortem brain tissue of people aged 79 to 99 years, obtained evidence that the formation of new neurons in the hippocampus occurs not only in healthy people but even in patients with cognitive impairment and Alzheimer's disease, although neurogenesis in the latter is significantly reduced compared with older people who do not have cognitive impairment⁵⁴.

Neurobiologists from the University of Jyväskylä (Finland) found during experiments in animals that prolonged aerobic exercise increases neurogenesis in the adult brain⁵⁵. The hippocampus of mice that ran long distances showed increased formation of new neurons after eight weeks.

HOW NOT TO LOSE NEUROPLASTICITY IN ADULTHOOD?

Scientists identify three main factors that affect neuroplasticity at any age⁵⁶:

● physical activity;

● intellectual load;

● nutrition.

A meta-analysis conducted by scientists from the University of Toronto (Canada) shows that physical activity increases the concentration of neurotrophic factors, substances that induce neurons to form new connections⁵⁷. Changes can be noticeable after the first session, and the effect lasts for a day or more.

Regular and intensive training maximizes neuroplasticity. However, we can activate the formation of new connections in the brain even with 30-minute walks in which the heart rate reaches 60 % of the maximum, provided, however, that we do it at least three times a week.

A study conducted at Pennsylvania State University (USA) showed that learning a second language leads to anatomical changes in the brain⁵⁸. They are expressed in an increase in the density of gray matter, which indicates the formation of new neurons, as well as in the appearance of more structured white matter bands (connections between nerve cells). These changes, which were observed in both young and old people, indicate the activation of two mechanisms underlying neuroplasticity: neurogenesis and the formation of new synapses.

Researchers from the University of British Columbia (Canada) conducted a meta-analysis of 21 studies, all of which examined the effects of meditation on neuroplasticity⁵⁹. Experts found 123 differences in the brains of people committed to meditative practices. For example, there was a cortex thickening (increased volume of gray matter) in the prefrontal area. This indicates the activation of neurogenesis in the part of the brain responsible for memory, planning, and self-control through meditation.

Among the nutrients that help maintain neuroplasticity in adulthood, scientists highlight the following:

1. FLAVONOIDS – compounds found in tea, berries, onions, and red wine. A diet rich in flavonoids is associated with better preservation of cognitive function in the elderly⁶⁰. Curcumin, which is found in turmeric root and has antidepressant, anti-inflammatory, neuroprotective, and antioxidant effects.

2. RESVERATROL – a substance found in the wine and juice of black grapes. Evidence suggests that consumption of this flavonoid can slow the age-related decline in intellectual abilities⁶¹.

3. OMEGA-3 – a polyunsaturated fatty acid found in large quantities of sea and river fish. Just 300 grams of grilled salmon or 3 grams of fish oil contain the daily norm. Studies suggest that omega-3 fights inflammation and stimulates neuronal growth factors⁶².

Based on these studies and others, the team of nutritionist Martha Clare Morris of Rush University Medical Center created the MIND diet to fight Alzheimer's disease. It can reduce the risk of disease by 54 %, which, researchers say, is superior to the Mediterranean diet⁶³.

The basis of this diet:

1) greens, vegetables and berries, olive oil;

2) beans;

3) whole grains;

4) fish;

5) wine/black grape juice.

The MIND diet also recommends limiting red meat, butter and margarine, cheese, sweets and candy, fried food, and fast food.

NEUROTRANSMITTERS ARE THE LANGUAGE THE BRAIN SPEAKS

Neurotransmitters are chemical substances that transmit signals between two nerve cells or between neurons and other cells in the body. They affect many psychological and physiological functions of the body, as well as mood, memory, learning ability, and concentration, regulate sleep, appetite, and vital signs: heart rate, breathing, digestion features, etc.

Neurotransmitters are often confused with hormones. This is not surprising, because their regulatory functions are very similar, and, in addition, many neurotransmitters have hormone-double: there is dopamine-hormone and dopamine-neurotransmitter, and noradrenaline-neurotransmitter and noradrenaline hormone, etc. Even though these substances have the same chemical formulas, they differently affect the body.

The main difference is that hormones are produced only in the endocrine glands, while neurotransmitters are produced exclusively by neurons. Therefore, the effect of neurotransmitters is limited to the nervous system, and hormones act on the periphery and cannot penetrate the brain they are hindered by the blood-brain barrier.

The difference between hormones and neurotransmitters with the same chemical formula can be seen in noradrenaline. The hormone noradrenaline is produced in the adrenal glands during stress. Its effect is similar to adrenaline, but it has a more pronounced vasoconstrictive effect and has less effect on the heart rate, a less significant effect on the smooth muscles of the intestines, etc. That is, the sphere of influence of the hormone noradrenaline is internal organs. It is controlling the body's response to stress.

At the same time, the neurotransmitter noradrenaline "reigns" in the brain: in stressful situations, it is responsible for the sense of excitement and risk enjoyment, increasing aggression and reducing anxiety. In its more "peaceful" hypostasis, it helps to memorize information better in training.

THE PRINCIPLE OF OPERATION OF NEUROTRANSMITTERS

At what point does the nerve impulse "lose" its electrical nature and "switch" to a chemical one? This occurs when the signal coming from the nerve cell body along the axon reaches an area called the synapse. The synapse is a contact point between the end of one projection and the beginning of another one or the cell membrane to which a signal is to be delivered. Between them, there is a space 10–50 nanometers wide, which is called the synaptic cleft.

The terminal along which the signal came is called presynaptic. Neurotransmitters are synthesized there: they are contained in small vesicles. Their release into the synaptic cleft occurs in response to reaching a threshold action potential, i.e., the nerve impulse shall be characterized by a certain intensity.

Once released, the neurotransmitter enters the synaptic cleft and contacts the receptors on the surface of the "receiving side" projection, the postsynaptic membrane. Receptor activation gives rise to a new nerve impulse, which continues its way (if there is contact between neurons) or causes the desired effect in the cell to which the signal was sent. However, a chemical signal can also inhibit the nerve impulse at the postsynaptic terminal. It depends on what the neurotransmitters do – excite or inhibit.

After the signal transmission from one terminal to the other, the neurotransmitter molecules left in the cleft are either quickly destroyed or "pulled" into the presynaptic terminal through special protein pumps. This is called the principle of neurotransmitter reuptake, and it is used in the creation of some drugs. The effect of many antidepressants is based on blocking the reuptake of the neurotransmitter serotonin, which is responsible for good mood. As a result, serotonin stays in the synaptic cleft longer, having the desired effect.

WHAT ARE NEUROTRANSMITTERS, AND HOW DO THEY AFFECT PEOPLE?

According to the effect that neurotransmitters have on the "receiving" nerve terminal, they are divided into excitatory: they increase the action potential and generate a new impulse, and inhibitory: block the action potential achievement in the postsynaptic nerve ending. Some neurotransmitters, such as dopamine and acetylcholine, can have both stimulatory and suppressive effects, depending on the type of receptors on the postsynaptic membrane.

Next, we will talk about several neurotransmitters that have a powerful effect on various aspects of human life, both physiological and psychological.

DOPAMIN is called the neurotransmitter of winners, and scientists describe it as one of the key factors of internal reinforcement. Its formation helps to remember positive experiences: for example, when a person tastes good food, receives praise, has sex, and achieves a goal. The dopamine release is followed by euphoria: the brain remembers it and motivates the person to have the positive experience again. Dopamine plays an important role in learning processes, and it is also involved in the regulation of muscle function. When dopamine production is impaired, so-called dopamine diseases, like Parkinson's disease and schizophrenia, develop.

ACETYLCHOLINE is the first discovered neurotransmitter. This substance plays a crucial role in the transmission of impulses in the autonomic nervous system, which regulates the functioning of internal organs. Its release decreases the heart rate, while digestion, on the contrary, becomes more active, the tone of bronchial smooth muscles increases, etc. Acetylcholine, which is produced in the brain neurons, is involved in motor activity regulation, as well as processes related to memory and learning. Its deficiency plays an important role in the development of neurodegenerative diseases, particularly Alzheimer's disease.

SEROTONIN is one of the most important regulators of a person's mood. Its release inhibits neurons in brain areas associated with negative emotions, such as resentment, frustration, and sadness. Therefore, serotonin deficiency is fraught with the development of depression, and depression treatment is aimed at restoring the synthesis of this neurotransmitter. Serotonin is also involved in reducing pain sensitivity, ensuring normal sleep, and regulating appetite, memory, and learning.

GLUTAMATE is the main excitatory neurotransmitter of the nervous system; its presence determines the speed of impulses between neurons and target cells. It plays a crucial role in the early stages of brain activity, regulating the processes of learning and memorizing. Excess glutamate leads to nerve cell death, and deficiency leads to decreased brain activity and chronic fatigue. An imbalance of this neurotransmitter is observed in many neurodegenerative diseases.

THE FORMULA FOR HAPPINESS AT THE MOLECULAR LEVEL

We may know nothing about which neurotransmitters "dominate" our nervous system at any given time. However, we all feel the consequences of this "domination." Euphoria, quiet joy, a state of sadness, depression, and apathy are all consequences of the total interaction of neurotransmitters, hormones, and molecules called neuropeptides.

Neuropeptides are the most numerous group of substances affecting our emotions, and the least studied to date. The word "peptide" in the name indicates the protein nature of these compounds, and "neuro" – the point of effect, i.e., the nervous system.

Different sources give different data on the site of neuropeptide synthesis. Some researchers suggest that only substances formed in neurons shall be considered neuropeptides. Others include regulatory proteins, which are also synthesized in other types of cells but can affect the nervous system.

Today, the list of neuropeptides includes several hundred different compounds. These include substances by which the hypothalamus regulates the pituitary gland (liberins and statins) and some hormones synthesized in the pituitary, such as oxytocin, adrenocorticotropin, and melanocortins.

A large group of neuropeptides directly related to emotional tone are opioid peptides: e.g., enkephalins, endorphins, endomorphins, dimorphins, and nociceptins. By acting on the corresponding receptors, they affect mood, distress tolerance, and pain sensitivity; their metabolism disorder is one of the key factors in the formation of addictions, depression, and mental disorders.

Neuropeptides, unlike neurotransmitters, tend to be more "long-playing" substances, since they do not break down soon after release, but can circulate in the body for several hours. It is neuropeptides that researchers attribute responsibility for the complex shades of feelings experienced.

Hormones and neurotransmitters act "targeted": a specific receptor – a specific result. And during their circulation in the body, neuropeptides have time to "shoot" at a variety of targets. And one molecule can affect several receptors at once, and vice versa, different molecules connect to the same receptor. As a result, we can experience a whole range of sensations that alternate with each other.

CONCLUSION

Our nervous system is a very complex mechanism, the functioning of which affects the quality of our lives. In turn, the work of all parts of the brain is affected by many aspects, including physical and mental activity and nutrition.

Unfortunately, most of us spend very little time and effort developing our brains and improving our thinking, which does not allow us to make full use of the powerful resources given to us by nature. So, what can you do to optimize brain function? The answer is simple: constantly keep it in good shape, and develop cognitive skills.

Training shall include both logical tasks and tasks provoking an emotional reaction. The range of exercises is very wide: from board games, chess, and puzzles to learning an instrument, writing poetry, and language courses.

In addition, scientists advise traveling more, talking to smart people, establishing interpersonal relationships, and building social bonds.

NEUROTRANSMITTERS AND NEUROPEPTIDES

CHAPTER 6
THE ENDOCRINE SYSTEM

THE "HORMONE" WORD CONCEALS A WHOLE WORLD OF HIDDEN AND OBVIOUS EFFECTS AFFECTING OUR MOOD, AND REACTIONS TO EVENTS, CONTROLLING OUR STATE OF HEALTH, AND KEEPING US YOUNG. EVERY SECOND OUR BODY PRODUCES THOUSANDS OF HORMONE MOLECULES – TINY MESSENGERS THAT HELP THE BODY TO FUNCTION AS A WHOLE. FAILURES OCCURRING IN THIS SYSTEM GRADUALLY LEAD TO ORGAN DYSFUNCTION AND THE DEVELOPMENT OF MANY DISORDERS AND DISEASES.

That is why it is so important to understand how our endocrine system works, what rules it obeys, and how our thoughts, physical activity, diet, sleep, and wakefulness patterns affect it. For example, if we know how chronic stress affects every organ, cell, and molecule, we are much more motivated to overcome negative thoughts, find effective practices to help us cope with stress, and create optimal conditions for maintaining physical and mental health.

HOW DOES THE ENDOCRINE SYSTEM WORK?

The hormone (endocrine) system has a clear hierarchy: there are "controlling" organs and "executing" glands. Hypothalamus is at the top of this hierarchy. This unique structure, located in the diencephalon, combines the properties of neural tissue and gland. Its cells are called neurosecretory cells. In response to a nerve impulse, they fire (like the cells of the nervous system) and start to synthesize hormones (like glandular cells).

The hypothalamus is a powerful "computer" connected to all the structures of the brain and spinal cord. It receives information about the body's internal environment (temperature, energy balance, water, and salt exchange, and blood pressure). And the "wires" coming from organs of senses inform the hypothalamus about events in the external environment. This is where nerve impulses are "translated" into the language of hormones. When the hypothalamus receives information that requires adjustment of the internal environment or behavior, it "turns" to its helper, the pituitary gland.

The pituitary gland, unlike the hypothalamus, does not claim to be the brain but is content with the title of a gland. But not an ordinary one, but the most important one. The pituitary gland is a "messenger" delivering the "decisions" of the hypothalamus to the executing glands. Three groups of hormones are produced in the hypothalamus: liberins, statins, and posterior pituitary lobe hormones. Liberins and statins are regulatory hormones: the former stimulates hormone formation in the pituitary gland and the latter inhibits it. Liberins and statins enter the pituitary gland through small vessels called the portal system and activate or inhibit the production of hormones affecting the body. Oxytocin and vasopressin are the hormones of the posterior pituitary gland. Although both hormones are synthesized in the hypothalamus, they are stored and released by the pituitary gland.

A total of about 15 hormones are synthesized in the pituitary gland. Some of them act directly on a particular gland. For example, thyroid-stimulating hormone stimulates the production of thyroid hormones, and adrenocorticotropic hormone stimulates the synthesis of adrenal hormones. Others have a systemic effect on the entire body.

For example, the somatotropic hormone of the pituitary gland activates bone growth in children and adolescents, affecting the growth sites in the tubular (long) bones, its deficiency is the cause of dwarfism. The somatotropic hormone is also one of the main "builders" of the body, it stimulates protein synthesis in connective tissue, and muscles, which promotes recovery after physical activity, helps to burn fat faster, etc.

The pituitary gland and hypothalamus together form the hypophyseal portal system. The total weight of these organs is barely six grams. Nevertheless, it is the control center not only of our body but also of our emotions, reflexes, potential for longevity, etc.

Hormones synthesized by the pituitary gland under the direction of the hypothalamus are brought with the blood flow to the endocrine glands: thyroid, thymus, pancreas, as well as to ovaries, testicles, and adrenal glands. In response to these hormonal "messages," the glands activate (or block) the production of their hormones, which causes the corresponding physiological effects.

Some pituitary hormones, such as growth (somatotropic) hormone, do without intermediaries – their biological effects are achieved through the direct hormone action on tissues. Other hormones of the pituitary gland, on the other hand, need "levers" to produce results, and the peripheral glands fulfill this role.

The sequential transmission of hormonal signals from the hypothalamus to the pituitary gland and the end gland is called the regulatory axis.

REGULATORY AXIS–PRINCIPLE OF DIRECT AND FEEDBACK

The regulatory axis mechanism can be traced in the example of the interaction between the hypothalamus, pituitary gland, and thyroid gland (hypothalamic pituitary thyroid axis). Regulation is based on the feedback principle, which can be positive or negative. The thyroid gland produces thyroid hormones: triiodothyronine, thyroxin, and calcitonin. They play a key role in the regulation of metabolic processes, in hematopoiesis.

In response to an excessive increase of thyroid hormones in the blood, the pituitary gland stops synthesizing thyroid hormones. As a result, the formation of thyroid hormones stops. This is an example of negative feedback. Conversely, if the level of thyroid hormones decreases, the hypophyseal portal system starts to stimulate their formation. It is positive feedback.

Another hormonal axis of the body, the gonadal-pituitary hypothalamic axis, connects the hypothalamic-pituitary pair with the reproductive organs. It starts with the synthesis of gonadoliberin in the hypothalamus, which, acting on the pituitary gland, stimulates the formation of two other hormones, luteinizing and follicle-stimulating. Targets for these hormones are the reproductive glands: the ovaries in women and the testicles in men. There is a synthesis of sex hormones – estrogen and testosterone. Both hormones are produced in men and women, just in different proportions (the female body has a synthesis of estrogen, and the male body has a synthesis of testosterone).

Different regulatory axes can affect each other. Stressful situations activate the hypothalamic-pituitary-adrenal axis (see details below), which is accompanied by increased formation of the corticoliberin hormone in the pituitary gland. Excess corticoliberin suppresses gonadoliberin synthesis. This leads to lower levels of sex hormones in the body. Therefore, sexual attraction is reduced, and reproductive function is suppressed under stress.

Thus, in the endocrine system, inter-regulation is possible not only between organs but also between entire "hormonal" axes. This gives our body a tremendous opportunity for close "communication" between various organ and tissue systems and causes its adequate reaction to external factors by activating or suppressing the functions of these very organs.

"STRESSAXIS": WHERE DOES THE STRESS COME FROM?

The hypothalamic-pituitary-adrenal axis is called the "stress axis" because it is responsible for the body's response to stressful situations, and its adaptation to changing environmental conditions. On the hypothalamic side, corticoliberin is involved in these processes, which activates the formation of adrenocorticotropic hormone (ACTH) in the pituitary gland. Bloodstream delivers ACTH to the adrenal glands, small paired glands located above the upper pole of the kidneys. They produce glucocorticoids (cortisol) regulating metabolic processes, stress hormones adrenaline, and noradrenaline.

Adrenal hormones are continuously produced in the body and affect different functions. However, their most pronounced effect is the ability to mobilize resources in stressful situations. While adrenaline and noradrenaline are more responsible for sharp stress reactions ("fight-or-flight"), cortisol is called the hormone of long-term or chronic stress.

FUN FACT

CHRONIC STRESS AFFECTS THE BODY AT THE GENETIC LEVEL

Scientists from the Weizmann Institute of Science (Israel) and the Max Planck Institute of Psychiatry (Germany) found that being under chronic stress affects the activity of more than 1,500 genes in body cells.

Experts studied gene expression in nearly 22,000 cells derived from the hypothalamus, pituitary gland, and adrenal cortex of mice. It was found that long-term exposure to stress changed the activity of 66 genes in the hypothalamus, 692 genes in the pituitary gland, and 922 genes in the adrenal glands.

Chronic stress, according to scientists, can affect the entire body and make it more vulnerable to the development of many diseases.

Cortisol in the adrenal glands is synthesized continuously, and its concentration fluctuates throughout the day. The highest level of cortisol is observed in the morning: it helps to move away from sleep, helps maintain energy, regulates blood pressure, and blocks excessive immune system activity (which is important for suppressing inflammation, allergic, and autoimmune reactions). However, in chronic stressful situations, the concentration of this hormone in the blood remains high. Elevated cortisol levels lead to increased anxiety, unease.

Evolutionarily, chronic stress was associated, for example, with food scarcity and "pushed" our ancestors to specific actions (search for food) helping to survive. Today chronic stress is most often caused not by problems of physical survival, but by various troubles at work and in the family, dissatisfaction with the financial situation, reactions to negative news in the media and the Internet, etc. That is, we do not mean stressful situations, which can be "resolved" by clear and specific actions, but constant anxiety, the source of which is mainly in our mind. In turn, elevated cortisol levels lead to increased anxiety and a further increase in the hormone concentration.

So, a vicious circle is formed, forcing us to react to the smallest troubles with an excess of negative, constantly reproducing some stressful events in mind. A consistently high level of cortisol leads to a whole range of unpleasant consequences. These include immune system depression, metabolic disorders leading to diabetes and obesity, hypertension, insomnia, depression, and accelerated aging.

HORMONE PRODUCING CELLS IN THE PERIPHERY

Besides the endocrine cells that make up the "official" glands, there are cells with the same function – hormone production but dispersed throughout the body. Scientists have counted more than 60 types of APUD cells (this is what endocrine-like cells are called), located in different organs. Cells that have hormonal activity but are not part of the "official" endocrine system, scientists called the diffuse neuroendocrine system.

The biggest concentration of hormone-producing cells is in the gastrointestinal tract: stomach, pancreas, large and small intestine. Some hormones (e.g., gastrin, produced by gland cells of the intestine) are mainly engaged in the regulation of digestion. But cholecystokinin, which is synthesized in the duodenum, affects both digestion and human behavior, preventing the development of depression.

The lion's share of serotonin, the hormone of good mood, is produced by the secretory cells of the intestines (60 to 80 % of all serotonin in the body). And in the pancreas, an exact analog of the somatotropic hormone of the pituitary gland is formed, which has the same effect on metabolic processes.

Kidneys, producing renin, have a hormonal "hobby," which raises blood pressure, and erythropoietin, which stimulates blood cell formation. The heart is also not to be immune to hormonal activity: here cardiac atrial natriuretic hormone is synthesized, causing the kidneys to remove sodium faster, and, respectively, water.

And even such an inert substance as adipose tissue also shows hormonal initiative, producing leptin. This hormone increases the sensitivity of cells to insulin (a pancreatic hormone that facilitates glucose penetration into cells). And in high doses (with severe obesity) leptin suppresses insulin formation, which leads to the development of type II diabetes.

EPIPHYSIS: THE GLAND DETERMINING THE COURSE OF OUR LIVES

Epiphysis (or pineal gland) stands apart from the organs of the endocrine system. It is called a "mystery" gland, because this tiny organ weighing less than one gram, located in the center of the brain, has been associated with clairvoyance abilities since antiquity. Modern scientists jokingly call the epiphysis a grey eminence.

As far as researchers know, this gland does not obey the orders of the hormonal "government" – the hypophyseal portal system, but, on the contrary, affects its activity. Due to the epiphysis isolation, and its independence from the influence of the hypophyseal portal system, scientists refer to the pineal gland as the organ of the diffuse neuroendocrine system, just like the hormonal cells of the intestine, kidneys, heart, etc.

The pineal gland consists of nerve cells, glial helper cells, and endocrine pineal cells that synthesize melatonin. Usually, higher levels of melatonin are observed in children, and its amount gradually decreases with age. This curious hormone is currently the subject of many studies. It has been found that it has a multifaceted effect on the body.

It is proved that it helps reduce the risk of cardiovascular disease⁶⁴, regulates the immune system and slows aging⁶⁵, prevents the development of cancer and inhibits the reproduction of tumor cells⁶⁶, helps normalize blood pressure, has a positive effect on metabolic processes, protects against depression and mental disorders⁶⁷. The key function of the epiphysis and its hormone melatonin is the regulation of circadian biorhythms.

REGULATION OF CIRCADIAN BIORHYTHMS

Most of the processes in our body are rhythmic. Every cell of the body is "equipped" with its clock, and our health depends on the proper "running" of all cellular clocks. Some biorhythms are quite independent: the heartbeat and breathing movements are performed with a certain frequency and only to some extent depend on external factors. However, most biorhythms are related to environmental rhythms, also called ecological rhythms.

Biorhythms that last less than a day are called ultradian: they include the rhythm of hormone secretion, alternating periods of vigor and fatigue during the day; the course of metabolic processes causing hunger and satiety, subordinates them.

Infradian rhythms are biorhythms lasting more than a day. Several studies have found that fluctuations in the level of stress hormones in the body (their synthesis, release into the blood, and excretion) correspond to a 21-day cycle⁶⁸. Infradian rhythms include lunar biorhythms, of which the menstrual cycle in women is a good example. During this period, which takes an average of 28 days, the body temperature, blood glucose levels, and the amount of fluid in the body change. There are studies indicating that the full moon increases the number of postoperative hemorrhages and myocardial infarctions⁶⁹.

The most important biorhythms in our lives are circadian (from Latin circadian – "during the day"). The work of hormonal, nervous, respiratory, digestive, cardiovascular, muscular, and immune systems is subject to circadian biorhythms; metabolic processes, tissue repair, physical and mental activity, susceptibility to stress, and much more are connected with circadian rhythms. Epiphysis and its hormone melatonin play a key role in the regulation of all these processes.

FUN FACT

OUR "INTERNAL" DAY IS LONGER THAN THE ASTRONOMICAL ONE

In 1962, French scientist Michel Siffre conducted a chronobiological experiment. Siffre had equipped a cave for a long-term stay with no sunlight. The experimenter's task was to study circadian biorhythms with no access to natural light sources. On July 16, the scientist descended into the cave. Throughout his time in isolation, Siffre notified his colleagues on the outside of his bedtime and waking moments, as well as what time he thought it was. The experiment ended on September 14, but Siffre's subjectively thought that it ended on August 20. It was estimated that even in the absence of natural light sources, the subjective duration of the day (sum of the duration of sleep and wakefulness periods) averaged 24.5 hours. At the same time, the longer the scientist was underground, the longer his subjective day felt. Repeated experiments led by Siffre showed that prolonged isolation (the second time the scientist spent 205 days in a cave) leads to the transition to a 48-hour day (36 hours of wakefulness, 12 hours of sleep).

Although the pineal gland is "hidden" deep in the brain, there is a pathway that allows the epiphysis to "learn" about nights and days and respond to changes in the light regime. How does it happen? Information about the light regime comes from the retina to a structure of the hypothalamus called the suprachiasmatic nucleus (SCN). Then the impulse is sent to the upper cervical sympathetic ganglia and from there it returns to the epiphysis, activating or inhibiting the melatonin production.

During the waking period, light striking the retina supports the activity of thousands of neurons in the suprachiasmatic nucleus. The nerve cells of this hypothalamic department produce a tremendous amount of biologically active substances, including neurotransmitters, hundreds of neuropeptides, cytokines, and various proteins. Most of these substances are related to the regulation of circadian biorhythms in different body cells.

During the night most SCN neurons are inactive, but some nerve cells send impulses to the spinal cord, then return to the epiphysis. Nerve endings that approach the pineal gland release the neurotransmitter noradrenaline, stimulating the melatonin formation in the pineal cells.

In addition, studies show that another neurotransmitter, dopamine, is also involved in melatonin synthesis regulation⁷⁰. Interestingly, dopamine receptors are absent in epiphysis early in the night and only appear closer to the awakening moment. Stimulation of these receptors inhibits melatonin production and makes it easier to wake.

As we age, the function of the suprachiasmatic nucleus as the main "driver" of rhythm decreases. This leads to impaired melatonin formation, sleep problems, and the flattening of many circadian rhythms.

LIGHT REGIME, SLEEP, AND MELATONIN

The human body produces about 30 micrograms of melatonin every 24 hours, and pineal cells synthesize about 70 % of this hormone at night. Melatonin levels start to rise about two hours before bedtime, peaking at an average of 2–3 am, and fall towards 5 am, reaching daytime levels between 7 and 8 am local light time⁷¹.

Sufficient melatonin production in the epiphysis is essential for healthy sleep: it not only determines sleep depth but also takes part in the regulation of sleep phase change. In a study at McGill University (Canada), scientists found two types of melatonin receptors in the brain – MT1, MT2, and MT3⁷².

MT1 receptors are activated during the REM sleep phase, accompanied by eyeball movement. This phase, during which a human dreams, is thought to play a key role in shaping long-term memories.

At the same time, melatonin synthesis is closely linked to the light regime. Bright light in the evening suppresses the production of this hormone, and light from gadgets, and street lighting entering the room during sleep, also negatively affects the melatonin synthesis in the epiphysis.

Besides excessive illumination in the evening, light sources in the room during sleep, sleep and wakefulness disorders, and working at night, other factors negatively affect melatonin formation in the epiphysis. These include a lack of physical activity during the day, chronic stress, and excessive caloric intake.

WHAT ARE THE CONSEQUENCES OF SLEEP DISORDERS AND MELATONIN DEFICIENCY?

Insufficient formation of melatonin in the epiphysis leads to several negative consequences, including an increased risk of cancer. A group of American scientists from the University of Texas found that people who live in regions with high levels of street artificial lighting at night have an increased risk of thyroid cancer⁷³.

According to the study, residents in areas with the highest nighttime light levels had a 55 % higher risk of this type of cancer than residents in low-light areas. Moreover, this connection was more pronounced in women. According to the report, this situation stems from the fact that the level of the female sex hormone estrogen increases due to melatonin deficiency, which creates conditions for cancer development. In addition, according to experts, malfunctions of the body's internal clock due to insufficient formation of melatonin is a favorable background for the emergence and multiplication of cancer cells.

Night work is another danger to health. A study conducted by scientists at Washington State University (USA) showed that disruption of circadian rhythms due to such a regimen increases the risk of DNA breaks and cancer development⁷⁴.

Lab results proved that the night shift altered the normal circadian rhythmicity of genes associated with the development of cancer. It turned out that the volunteers with the night schedule had significantly more breaks in the DNA structure than the control group. Moreover, the former demonstrated a strong vulnerability of blood cells to radiation-induced DNA damage.

Other negative effects of melatonin deficiency associated with sleep and wakefulness disorders include accelerated aging, immune suppression, increased risk of metabolic disorders (diabetes, obesity), hypertension, Alzheimer's, and Parkinson's diseases⁷⁵.

HOW TO SLEEP TO MAINTAIN MELATONIN FORMATION IN THE RIGHT AMOUNT?

A few rules can help ensure optimal conditions for melatonin formation during sleep.

1. Train yourself to go to bed and get up at the same time, try to stick to this regime not only on weekdays but also on weekends.

2. Hung black-out curtains over the windows of the bedroom, so they do not let light in.

3. Do not watch TV and stop using gadgets at least one hour before bedtime.

4. Do not smoke or drink alcohol at least four hours before bedtime.

5. Evening meditation will help to reduce stress hormones, calm the brain, and put it to sleep.

6. Avoid eating junk foods in the evening, as well as foods rich in spices. Include complex carbohydrates in your dinner, such as cereal, and vegetable salads.

7. Take a warm bath shortly before bedtime.

8. Move more throughout the day: aerobic exercises and yoga in the morning and daylight help you fall asleep faster in the evening.

FUN FACT

REM SLEEP PLAYS AN IMPORTANT ROLE IN LIFE EXTENSION

Experts from Stanford University have found that REM sleep is important not only for memory and other cognitive functions of the brain but also for life expectancy. The study found that problems with REM sleep increase the risk of early death from all causes: reducing REM sleep by just 5 % increased the risk of premature death by 13 %. The experts noted that the reduction in the duration of REM by 15 % is particularly dangerous.

HORMONES AND AGING

The work of the hormonal system has a powerful effect on all body functions. Health and youth depend on how effectively each cell of the endocrine system works (from the hypothalamus to the glandular cells in the periphery). However, as we age, the hormonal system often malfunctions, accelerating aging.

ADRENAL SYSTEM AGING (STRESS RESPONSE)

One of the reasons for cognitive impairments and age-related changes in the immune system is thought to be an increase in steady levels of glucocorticoids, the steroid hormones of the adrenal cortex (regulators of carbohydrate, mineral, and protein balance).

Glucocorticoids increase bone fragility, reduce the number of new bone cells, and increase protein breakdown in muscles, leading to muscle failure. Activation of the hypothalamic-pituitary-adrenal axis increases significantly with age, so cortisol and ACTH (anterior pituitary lobe hormone that affects glucocorticoid synthesis) are used as biomarkers of aging.

Elevated cortisol levels are also associated with age-related illnesses such as Alzheimer's disease, cardiometabolic syndrome, and hypertension.

A decrease in the effectiveness of stress response is due to a drop in adrenaline and noradrenaline levels. Moreover, the ability of noradrenaline to act on immune cells and thereby activate pro-inflammatory mechanisms decreases with age, which leads to a weakened response of the immune system to external stimuli.

AGING OF THE REPRODUCTIVE SYSTEM

Normally, estradiol and other sex hormones help to improve memory, and cognitive functions, maintain bone mineral density, and have a protective effect on those neuron areas that are destroyed by glucocorticoids under stress. Skin elasticity and muscle tone are greatly affected by estrogen, which is why after menopause women have so many wrinkles, skin becomes dehydrated, muscular frame weakens, pigmentation appears, and blood vessels become visible. Estrogen deficiency leads to osteoporosis, impaired calcium metabolism, brittle bones, increased likelihood of fractures, and long healing.

Testosterone increases facial and body hair growth, but its high levels also contribute to baldness. After the end of the reproductive period, the activity of the entire hormonal axis weakens, leading to devastating consequences for the nervous, immune, and endocrine systems and systemic body aging.

THYROID SYSTEM AGING

Thyroid hormones have been shown to affect overall tone, have anti-depressant properties, and lower cholesterol levels. Thyroid function decreases with age, it means thyroid hormones can be used in therapy for older people. However, there are discussion papers showing that reduced thyroid function after 60 years may be a determinant of longevity. In general, scientists agree that even low-grade hypothyroidism (reduced thyroid function) leads to atherosclerosis, and reduces hemoglobin and immunity. But the fact remains that both the reduction and overproduction of thyroid hormones lead to cardiovascular diseases, especially in the elderly.

Understanding how the body works, regular monitoring of substances that are biomarkers of aging, diagnosis of well-being, and timely correction of indicators by medical and drug-free methods under the doctor's supervision will help to reduce the biological age and timely replenish the body's resources, turn off aging effects, maintain body functions as productively as possible.

CONCLUSION. HOW WE CAN AFFECT HORMONE PRODUCTION?

The close connection between the nervous and hormonal systems not only underlies favorable effects that improve life but also often becomes the basis for the origin of bad habits.

For example, when an untrained person decides to do sports, at first it can be followed by a release of stress hormones. They imagine an unfamiliar environment, discomfort, and such thoughts result in cortisol production.

As a result, the heartbeat quickens, and blood pressure increases – the person is already experiencing the full range of negative feelings they think they will have to deal with in the future. This clutch between thoughts and hormones often becomes an obstacle to any change in life.

But if the person does overcome fear and go to the gym, coping with the first negative feelings that are natural for anyone who leaves their routine, their body soon begins to receive hormonal "bonuses." Endorphins, which are produced with physical activity, make you feel good and happy. The thought of training does not release stress hormones but rather produces endorphins, which increase the motivation to keep exercising.

This body's ability to change hormones not only in real-life situations but also when thinking about them lies at the heart of self-programming. The problem is that the body gets used to the condition it is in most of the time, even if this condition is negative.

For example, cortisol, noradrenaline, and melatonin are released in response to resentment. The release of these hormones into the bloodstream triggers a chain of chemical reactions that irritate certain nerve endings. As a result, we feel fear, anger, and sadness, which are the building blocks of resentment. If we managed to solve the situation, hormones that provoke negative feelings cease to be produced. But when a person keeps thinking about the resentment, hormones continue to synthesize: the endocrine system does not feel the difference between the real event and thoughts about it.

When thoughts (and thus hormonal responses) persist from day to day, the body gets used to this state on a chemical level. The resentment (anger, guilt, etc.) becomes a comfort zone, while joy and corresponding hormonal background become an outlier.

This "negative" body chemistry is the reason why many good initiatives based on the right actions fail to produce positive results. Therefore, many life improvement practices primarily involve working with thoughts.

It is recommended to first experience positive events at the level of mind, adjust the body to "good" hormones, and then perform actions that reinforce the positive result and allow the formation of positive dynamics at both the biochemical and physical levels.

MAIN HORMONES

CHAPTER 7
FEELINGS AND EMOTIONS

OUR WHOLE LIFE IS A PALETTE OF EMOTIONS AND FEELINGS. MOMENTS ARE REMEMBERED PRIMARILY BECAUSE OF THE POWERFUL EXPERIENCES WE HAVE HAD. IN ESSENCE, POWER OVER FEELINGS AND EMOTIONS IS POWER OVER YOU. BUT IT IS NOT ENOUGH TO CONTROL THOUGHTS, BECAUSE FEELINGS AND EMOTIONS DO NOT COME ONLY FROM THE BRAIN.

It is a whole flow of nerve impulses piercing the body, waves of various chemicals washing over every cell. Sensory and emotional experiences are the performance of an orchestra of hormones, neurotransmitters, and neuropeptides. When it comes to prolonging life, it is important to reflect: how can I avoid becoming a hostage to negative feelings and emotions and help my mind and body "switch" to a stable mode of positive experiences?

BIOCHEMICAL STYLE OF DIFFERENT EMOTIONS AND FEELINGS

Emotions and feelings are recognizable: as early as the first months of life, the child starts to recognize the connection between the mother's facial expressions (a smile or frown) and her behavior towards them at the moment (gentle, rude, calm).

Even very different people, regardless of personality, upbringing, or cultural background, feel and express the same emotions and feelings in a very similar way. Because they are based on the same neurochemical mechanisms, differing in characteristic style at the level of physiological manifestations.

Let us find out what's behind all these feelings.

JOY AND HAPPINESS

Positive emotions and feelings that we can experience, range from the simple pleasure of a cup of coffee to the euphoria of a hard-won victory.

Imagine that you had a long journey towards a goal: preparing for a competition / working on a complex project / writing a thesis. Finally, you are holding the coveted trophy / your boss praises you and rewards you / your colleagues congratulate you on your degree. How do you feel? Not just light joy, but real euphoria! This jubilation is what dopamine, the neurotransmitter of encouragement, is responsible for.

However, dopamine levels can be increased (albeit slightly) without much effort, e.g., through delicious food. And there is a catch: in the early stages of evolution, food was often gathered at great risk to life, and the dopamine dose, in case of luck, was released well deserved. But now all we have to do is go to a store or open the fridge.

This is why people living on the principle of delayed gratification have an evolutionary advantage today: the person preferring to "earn" the dopamine "medal" by achieving real results in sports, careers, studies, etc. is much more socially successful than that one, who simply get high from a slice of pizza or winning a computer game.

Serotonin is responsible for feelings of simple pleasure, and joy. You do not need to conquer Mount Everest for this neurotransmitter to be released. It is enough to go outside in sunny weather, take a walk in the park and get a good sleep.

The quality of serotonin positivity differs from the dopamine "explosion": instead of violent jubilation, there is a calm surge of energy and vigor, that very feeling that "all is well." Serotonin not only affects our mood, but it also makes our brain more curious and receptive to new information, makes us resistant to stress, and keeps our muscles nicely toned. It is noted that socially successful people have consistently higher serotonin levels, which ensures emotional stability and self-control.

Serotonin production requires sunlight and tryptophan, an amino acid that is found in abundance in red meat, hard cheese, egg powder, and soy, and lesser amounts in caviar, sunflower seeds, chicken, turkey, calamari, sesame, and peas. Serotonin deficiency is fraught with depression; the effects of most antidepressants are due to an increase in its concentration in nerve networks.

Other "colors" making up the "palette" of positive feelings are opioid peptides. Among the effects they have are the joy of exercise, sexual satisfaction, and the pleasure of food. That is, opioid neuropeptides enable us to enjoy different aspects of being, experiencing all shades of joy and pleasure. In addition, their elevated levels help to tolerate pain better and speed up the regeneration of damaged tissues.

Unfortunately, stimulation of these peptides is also responsible for the most severe forms of drug addiction: substances such as morphine and heroin have a stimulating effect on opioid receptors, causing rapid addiction and a dramatic suppression of the synthesis of our joy neuropeptides.

The experience of joy, pleasure, and happiness, i.e., the circulation of dopamine-serotonin and opioid-peptide molecules in the body, has beneficial effects on the body not only in the short but also in the long term. Researchers from Singapore conducted a study and found that people who feel happy, enjoy life, and have hope for a better future live longer⁷⁶. The experiment found that the group of people who considered themselves happy had a 20 % lower mortality rate than the group of participants who rarely experienced happiness. Another study conducted by experts at University College London found that people who feel happy, fulfilled, and satisfied with their lives on the most ordinary days have a 35 % lower chance of dying prematurely⁷⁷.

FUN FACT

SPIRITUALITY AS THE WAY TO HAPPINESS

A study by the Pew Research Center found: 36 % of people who are actively involved in religious activities feel happy and healthy. At the same time, among those who consider themselves believers but are not religiously active, as well as among those who do not consider themselves members of any denomination, 25 % are happy.

However, experts emphasize: the results of the study cannot be considered evidence that it is the active religious activities within any denomination that makes people happy. According to experts, perhaps it is people's initial view of life that motivates them to participate in religious activities. Being active in the community, and doing charity contributes to the formation of many social ties, and the development of new friendships, which plays an important role in supporting the view of the life of a happy person.

In addition, researchers say that spirituality does not necessarily imply belonging to any religious associations. Mindfulness practices, and meditations – all of this reduces stress levels, helps to think positively, and greatly increases the chances of being happy and healthy. Yongey Mingyur Rinpoche, author of "The Buddha, The Brain, And the Science of Happiness," writes about this. He tells about studies that have shown that during compassionate meditation, the activity of brain areas responsible for feelings of happiness increases by 10–15 % – and this happens during the first classes for beginners. For those who devoted many hours to practice, "happiness neurons" become 700–800 % more active.

Experiencing joy and happiness is not only pleasant, but also profitable: diseases recede in front of a positive attitude, and early aging fades away. The earlier a person learns to positively perceive any situation, to see a favorable outcome in each event, the stronger will be the foundation of their health.

LOVE AND PASSION

When we speak of love, we often mean a whole range of emotions and feelings, from passion to quiet affection and tenderness. Accordingly, the neurochemical provision of each shade of the love spectrum will be different.

Phenylethylamine is responsible for the feeling (euphoria) of first love. Several studies show that this substance begins to intensely synthesize by nerve cells when a person falls in love. Phenylethylamine acts both as a neurotransmitter, transmitting nerve impulses, and as a neuromodulator, a substance activating the production of dopamine and noradrenaline. Phenylethylamine is believed to be the same love molecule that causes "butterflies in the stomach," making us focus all our thoughts and desires on the object of love.

When we "melt" under the touch of a loved one, and feel pleasure just by meeting their eyes, it means that neuropeptides from the endorphin group have found their receptors. However, not only endorphins but also other opioid neuropeptides are involved in forming the euphoria of being in love, making us forget about sleep and food, and suppressing painful sensations so that we can float in pink and sweet neuropeptide clouds all day.

Another love hormone is oxytocin. A consistent increase in its level indicates the transition of the relationship to the stage of quiet trust. Moreover, "oxytocin flashes" in the body occur during kissing and orgasm: the higher this hormone concentration, the more sensitive the skin receptors are to touch.

Vasopressin is the hormone of loyalty and affection. This pituitary hormone level is elevated in animals and humans inclined to monogamy. Excitation of oxytocin receptors provokes the desire to be faithful and take care of love objects and offspring.

The biochemical "love cocktail" also includes many other molecules. These are both sex hormones, responsible for desire and attractiveness, and pheromones, which are produced by gland cells of the skin to form the "scent of attraction." Dopamine, which we already know, plays the most important role in relationships. Increased concentration of this hormone allows for overcoming obstacles to love and gives euphoria in achieving the goal. Moreover, the infatuation period is characterized by "serotonin waves": joy arising when you feel that feelings are mutual is replaced by a decline in a mood when in doubt.

The key to a long life and slow aging is not only sports and good nutrition, but also relationships: feelings of love, intimacy, trust, and affection help to cope with negativity and stress, improve mental health and enhance the quality of life. A study conducted by Harvard scientists among 80-year-old spouses found that people living in happy marriages report lower levels of pain experienced⁷⁸. And even if the pain increased on some days, their mood was not spoiled – partner support seemed to soften discomfort. But those who lived in unhappy marriages felt more physical and emotional pain.

Another 2015 study showed that women who felt attached to their partner were less depressed and happier in their relationships after two and a half years and had a better memory than ladies whose married life had lots of conflicts⁷⁹.

CALMNESS

Gamma-aminobutyric acid is a key inhibitory neurotransmitter of the nervous system. GABA, like a firefighter, pours an icy stream on flaming centers of excitement, encouraging neurons to slow down. GABA extends its calming effect to many processes, including the emotional sphere. Sufficient synthesis of GABA helps to adequately respond to stress, to recover quickly, not to worry, and keep calm.

GABA deficiency underlies many neural disorders, the most common of which is epilepsy. In this disease, gamma-aminobutyric acid deficiency leads to an excitation focus in the brain, which periodically "resets" during seizures. Insufficient synthesis of GABA also leads to increased anxiety, decreased stress tolerance, fears, and detraction.

FEAR, ANGER, IRRITATION

Most of the hormones causing negative emotions and feelings are synthesized in the adrenal cortex. In essence, it is a kind of "emergency safety system" built into the body in case of life-threatening situations.

The first member of this system is adrenaline, the hormone of fear. Its release is accompanied by an increased heart rate and deep breathing, the muscles fill with energy, and attention is focused on the problem causing stress. Decomposition processes dominate the body, which is due to the increased demand for energy. The second participant is noradrenaline, a stand-in for adrenaline. Its effects are similar to the latter but less pronounced. It has less effect on the heart muscle and metabolism. At the same time, its effect on blood vessels is stronger than that of adrenaline: vascular spasm, occurring upon stimulation of noradrenaline receptors, leads to a significant increase in blood pressure. At the emotional level, the release of noradrenaline is accompanied by anxiety rather than acute fear.

And finally, cortisol, the hormone of steady stress. Constant synthesis of this hormone in the adrenal glands is necessary to maintain normal body tone. Normally, its concentration changes during the day: maximum in the morning, minimum at bedtime. It is cortisol that helps us adapt when we face various stressful situations, to adapt to new circumstances – it is a kind of damping bed. Cortisol increases blood glucose levels and stimulates muscle breakdown and fat synthesis.

In the short run, the effects of cortisol help to mobilize forces and cope with the problem. If we are talking about chronic stress, such as living with constant feelings of irritation, anxiety, anger, and guilt, it is cortisol that turns into a worm that undermines our health. It suppresses immunity, increases bone fragility, activates the aging process, and provokes obesity and other diseases.

WHAT ARE THE DANGERS OF EMOTIONAL SUPPRESSION?

If the long-term experience of negative emotions harms health, it does not mean we should suppress them. Many studies have shown that when a person blocks their feelings, they can cut off their nose to spite their face. Experts from the Harvard T.H. Chan School of Public Health and the University of Rochester have found that people who hold back their emotions have a more than 30 % increased chance of premature death from all causes, and a 70 % increased risk of developing cancer⁸⁰.

Unexpressed emotions, whether anger, sadness, grief, or frustration, are also stressful to the body, and therefore they can affect physical and mental health. It is known, for example, that holding back feelings and avoidance of them are associated with high blood pressure, memory problems, and self-esteem issues. Overall, according to psychologists, the risk of depression, anxiety disorder, diabetes, and heart disease increases.

Scientists from the University of Texas found that when we suppress our emotions, we intensify them⁸¹. In the experiment, a group of people were asked to control their emotions while watching disgusting movie scenes from "Monty Python's The Meaning of Life" (1983) and "Trainspotting" (1996). Later, as the researchers observed, these subjects were more aggressive than the control group, which did not need to restrain themselves.

You can stay mad at someone or something, but suppress your feelings and not say what is annoying you, but this can cause an emotional breakdown. For example, if someone cuts you off while driving, you will be able to get so angry that it will provoke an accident. This overreaction is the body's way of releasing pent-in emotional energy.

How to learn to manage strong emotions? Psychologists recommend the following steps.

1. EMOTION RECOGNITION. You can have different feelings: sometimes, for example, it is not just anger or sadness, but something more complicated. It is important to find and understand the underlying emotion behind all the feelings. Ask yourself: "Why do I feel this way? Why am I reacting like this?" The process of identifying and describing this emotion will help in its expression.

2. OBSERVER POSITION. If there is no possibility of immediately solving a problem that causes strong emotions, for example, during an argument, then psychologists recommend taking the observer position. Watching from the sidelines means looking at the situation as if you were not part of it. It allows you to understand what the other person is thinking and what makes them behave in a certain way, helps you get to know that person instead of taking their actions personally and becoming angry or disappointed.

3. ANALYSIS AND RATIONALIZATION. To understand your emotion, you should analyze how you reacted to the situation and dealt with it. Think about what caused you to have a strong emotional reaction, and what ways of problem managing exist.

4. PHYSICAL EXERCISES AND MINDFULNESS. Mind-body exercises will have a positive effect emotionally. A 2019 study by Chinese scientists found that people who experience strong emotions do better at managing them after doing aerobic exercise: jogging and mindfulness⁸².

MIRROR NEURONS AND EMOTIONS

Our brains have perfect hypersensitive sensors that instantly recognize the slightest shades of feelings and emotions of the people around us. Special cells called mirror neurons give our nervous system such abilities.

Mirror neurons were discovered relatively recently – in 1992. The discovery of "imitation and empathy cells," made by Italian researcher Giacomo Rizzolatti, was immediately dubbed by the scientific world as one of the key breakthroughs in neurobiology in recent decades. At the same time, there were prerequisites for this discovery before: they were associated with the discovery of some strange motor neurons.

Nerve cells responsible for motor activity were traditionally considered by scientists to be "muckers" capable only of following orders received from the "elite" neurons of the cortex and sensory organs. For example, visual neurons directly "see" a stone on the road, while motor neurons only receive a signal from them to "find another route," but they remain "blind" at the same time.

The more surprising is the discovery that about 20 % of motor neurons play by completely different rules: they fire (show activity) not only when you act, but also at rest. And even during motor activity, they behave unpredictably: they fire during one movement, but not during another one, which is very similar.

After several years of observations and experiments, the researchers were able to compile a list of "oddities" of these neurons:

● they react only to move with purpose: if you reach out to take a cup of tea, they fire. And if you make the same movement, but with no purpose, there will be no activity;

● they are activated when we see objects with which we can interact (movement does not occur, but it can happen). For example, they are firing when we look at a cup from which we can drink, or a pen lying on the table with which we can write. Neurons allow us to sort of scan our surroundings with an ulterior motive, detecting objects that we can do something with. It is important that we already have experience interacting with the object (or have seen it used by others) – neurons will not respond to unfamiliar objects;

● they are firing by observing another person performing an action we understand. If we see someone drinking tea, these neurons will react to the action as if we were taking the cup and drinking the tea ourselves. And visual neurons respond not only to the actions of others occurring in reality but also to images – drawings, and videos. For this ability to "reflect" actions, creating in the brain a virtual image of the action performed, nerve cells were called mirror neurons;

● they do not respond if the movements of the observed subject are not part of our "motor repertoire," that is, the list of actions that we are familiar with at the physical level and whose purpose we understand. For example, the mirror neurons of a person who has ever danced will unload when watching another dancer, because what is happening is part of their "motor repertoire." Those who are far from dancing can get aesthetic pleasure from watching each move, but their mirror neurons will be at peace.

Thus, mirror neurons are very unusual cells that combine the functions of motor and visual neurons. Moreover, there are mirror neurons capable of responding to sound stimuli as well. They are firing when we hear sounds characteristic of certain activities, such as the sound of a spoon on glass walls that occur when we drink tea.

Mirror neurons help make sense of what others are doing. This understanding is needed to select the options for possible responses that are most appropriate to the situation. This makes any action of others meaningful to us and our actions meaningful to them. Thus, creating a common space of action.

How are mirror neurons related to emotions? Looking at the facial expression of a statue created thousands of years ago, or a person from a fundamentally different culture, we can easily consider their emotional state. What is the reason for the same facial expressions? The fact is that originally most facial expressions associated with basic emotions (fear, disgust, joy, sadness, anger) were designed to convey information related to survival to others. For example, disgust was originally a reaction to low-quality food: the expression that appeared on the face of a person who tasted spoiled food was instantly read by others, and they understood that it was not worth eating. The brain part responsible for the adverse response is called the insular cortex, where the neurons responsible for the sense of taste and smell are located. Moreover, signals about the condition of internal organs come here. Irritation of this area leads to nausea and vomiting, as well as discomfort in the mouth and throat.

That is why disgust, no matter what caused it – the touch of an unpleasant person, the strong smell of sweat, bits of food in someone's beard – causes the same reaction. There is a desire to pucker up the mouth, wrinkle the nose, spit, and in the case of strong disgust there may even be retching – exactly how we behave when we feel the taste of spoiled food.

Studies have shown that the insular cortex is rich in mirror neurons that respond to the wry face of another person as if we were experiencing it ourselves. The same physiological reactions may occur, including nausea and vomiting. Mirror neurons allow us to instantly read other emotions as well, experiencing them on a physiological level. A spasm of fear on the interlocutor's face, which creates a release of adrenaline (dilate pupils, pallor, frozen facial expressions indicating physical readiness to run or attack), will immediately affect our condition, in turn leading to an adrenaline surge. And it will happen in a fraction of a second, even before we understand the reason for the interlocutor's fear. The feeling of joy on another person's face is read by mirror neurons as a message of "all is well and calm" – and our body relaxes in response.

Importantly, basic emotions are recognized and reflected reflexively, essentially without our consciousness, because they are part of the brain's built-in survival mechanism. More complex emotions, such as empathy for pain, often depend on the situational context and personal qualities. Our mirror neurons will easily reflect someone else's suffering if it is familiar to us (it's easy to understand how someone with a toothache feels if we have experienced it ourselves). However, everyone's sense of compassion manifests itself differently: some may empathize with almost everyone, others – only the closest, and the suffering of unpleasant people may even satisfy someone. Recognition of some emotions depends on experience: a woman who has children easily "reflects" (on an emotional and physical level) the feelings of a young mother. We have a better chance to understand a person who suffered a loss in a similar situation, etc.

CONCLUSION: HOW TO DEVELOP EMPATHY?

Empathy is the ability to easily recognize another person's emotions and be able to empathize with them. Most of us do not need to go through training and read books explaining how to become an empath: a system of mirror neurons, evolutionarily "embedded" in the brain, allows us not just to see and somehow evaluate the feelings of the interlocutor, but, in essence, to stand in their place, to share their feelings. This is especially true for basic emotions: even if a person controls their feelings, our built-in "mirrors" only need a fleeting facial movement to recreate a picture of the emotions raging within them.

According to Giacomo Rizzolatti, the discoverer of mirror neurons, these nerve cells "allow us to grasp the minds of others not through conceptual reasoning but through direct simulation – by feeling, not by thinking."

Why is it that some people use this gift successfully, while others are constantly deceived about the feelings of their interlocutors? Can the mirror system let us down? The function effectiveness of mirror neurons depends primarily on mindfulness, both of oneself and others.

For example, if you look closely at the interlocutor, mirror neurons receive maximum information, allowing you to "feel" what is going on inside them. At the same time, extraneous thoughts, such as the impression we make on others, prevent us from focusing on the other person. And if some information does get into our mirror system, we may simply not notice it, because our sensations occupy us much more. At times people can recall that during a conversation with a person "something warned them," they had a bad feeling, but they suppressed it because they wanted to believe, for example, in the decency and sincerity of the interlocutor.

So how do we "develop empathy"?

● "Empathy pimping" is mindfulness training to give maximum "food" to mirror neurons. It is necessary to be able to focus on the other person's facial expressions, posture, and gestures, and even "smell" them. But do not try to conclude with the help of reason: it is more important to listen to your feelings, to the slightest changes within yourself. It is this "mirroring," which allows us to understand a person's real feelings and intentions, that underlies the empathy needed to succeed in society, whether in a romantic relationship or business.

● It is important to remember the other side of "mirroring": the effect of our feelings on other people. A sincere smile and relaxation will instantly "reflect" inside the interlocutor, increasing the chances of their disposition to us, and tension will respond with wariness: an attentive person's "sensors" can easily detect insincerity gestures. Therefore, the more harmonious personality, the smaller the gap between feelings and intentions, the more unambiguous signals will be interpreted by others, and the more accurate will be the impression of you as a person who can be trusted.

● The more sensations we have experienced in life, the wider the range of feelings our mirror neurons can recognize. After all, in addition to the basic emotions recognized even by a young child's mirror system, there are many complex emotional states. Traveling, communicating with different people, and constantly getting new experiences, we expand the palette of colors of our mirror system, increasing its chances of identifying the smallest shades of feelings of another person, thus multiplying the ability to empathy given to us by nature.

CHAPTER 8
IMMUNE SYSTEM

"HE HAS GOOD IMMUNITY," WE SAY OF A PERSON WHO RARELY CATCHES A COLD, AND SHOWS AN ENVIABLE IMMUNITY TO SEASONAL ATTACKS OF MALICIOUS GERMS. BUT PROTECTION AGAINST EXTERNAL THREATS – AGGRESSIVE VIRUSES OR BACTERIA – IS NOT THE ONLY FUNCTION OF THE IMMUNE SYSTEM.

Recognizing internal dangers, such as mutations in DNA that can lead to cancer, is also the responsibility of our immune system. At the same time, numerous studies showed the imbalance of our body's defense mechanisms, the violation of the process of recognizing useful and harmful substances, and our and foreign structures underlie the development of many diseases.

If the immune system perceives harmless particles in the food or air as aggressors, allergic reactions occur. And problems with "recognition" of own tissues lead to the development of autoimmune diseases – the "immunity against the host" reaction. If previously such diseases included a narrow group of pathologies, today it is proved that the spectrum of disorders is much wider.

Studies show that autoimmune aggression is a factor in the development of diabetes, Alzheimer's disease, and many other diseases.

Moreover, chronic inflammation in the body, which is also associated with the malfunctioning of our immune system, is now considered one of the key causes of aging. Therefore, understanding how the immune system functions and how to support it is essential for a person seeking a long, healthy life.

HOW DOES THE IMMUNE SYSTEM WORK

Our body has several levels of protection against the invasion of foreign agents:

● external barriers – skin and mucous membranes. They are a mechanical obstacle in the way of aggressors, as well as a "reservoir" of several protective factors – chemical and biological. For example, foreign bacteria viability is reduced upon contact with the lysozyme contained in saliva, and to an even greater extent when exposed to the aggressive gastric juice. In addition, skin and mucous membranes contacting the external environment are covered with biofilm, a shell of friendly bacteria. Biofilm protects the body through a whole range of mechanisms. There is such a characteristic of symbiotic (friendly) microbes as antagonist activity – the ability to compete with "foreigners" for a place on the skin or mucous membranes. Beneficial bacteria also synthesize "natural antibiotics." For example, lactobacilli in the small intestine and the vagina produce lactic and acetic acids that inhibit the growth and reproduction of foreign microbes;

● innate (passive) immunity – protective factors that a child receives from his or her mother without direct contact with foreign agents;

● acquired (adaptive) immunity – several protective mechanisms that are formed during direct contact with various factors and contribute to the formation of individual immunological memory.

HOW DOES INNATE IMMUNITY WORK?

Immediately after birth, the baby's body is already "tuned" to recognize a certain range of dangers. The innate immune system can be triggered, first, by molecules produced by certain microbes, and second, by substances produced by cell damage.

The main mechanism by which innate immunity copes with the threat is phagocytosis – the absorption of the microaggressor or damaged cell by an immune cell (phagocyte). Immune system cells such as neutrophils and macrophages act as phagocytes.

Neutrophils are a type of white blood cells, leukocytes, which circulate in the bloodstream. When there is a danger signal (of foreign microbe or damage), neutrophils are immediately sent to the focus.

Macrophages are immune cells that "live" in tissues. In addition to their ability to absorb uninvited guests or damaged structures, they activate adaptive (acquired) immunity by "reading" the characteristics of the foreigner and sending chemical messages to their fellows. A kind of macrophage is mast cells⁸³ living also in mucous membranes. They contain granules with substances that activate the inflammatory process in the body and play a role in the development of allergic reactions.

INFLAMMATION IS A DEFENSE MECHANISM THAT CAN DESTROY HEALTH

The most important mechanism by which the innate immunity protects the body is inflammation. Its task is to form a barrier between the area damaged by mechanical or chemical trauma, microbial invasion, and healthy tissues.

Moreover, immune cells involved in inflammation send chemical signals that activate the migration to the focus of other factors that contribute to the destruction of pathogens, cleaning the site of dead cells and microbes, and healing of injured tissues. As the damaged area recovers, the immune system triggers a reverse process to help suppress inflammation.

It is the right balance between the processes of activation and suppression of inflammation that characterizes the work of a healthy immune system. However, some factors disrupt this process, shifting it toward the development of chronic inflammation. Among them are frequent stress, a sedentary lifestyle, obesity, and body aging. In the body of an elderly person, the number of immune cells suppressing inflammation decreases, and the number of immunocytes provoking inflammation increases. As a result, there are conditions for the development of many chronic diseases belonging to the age-related category (various metabolic disorders, diabetes, atherosclerosis, cancer, dementia).

The role of chronic inflammation in accelerating the aging process has been proven in numerous studies. Scientists from the University of Madrid have found that energy deficiency in immune cells leads to accelerated body aging⁸⁴. In experiments on mice, specialists destroyed mitochondria – cellular "batteries" – in immune cells responsible for inflammation. As a result, mice at seven months of age began to look and act like older animals: they developed muscle weakness, cognitive functions suffered, metabolic shifts characteristic of old age, and vascular disorders appeared.

In addition, the rodents began to show pronounced inflammatory reactions: the immune system showed excessive aggression, which led to even greater tissue damage. After the experimental animals were injected with drugs that helped restore mitochondrial function in immune cells, they began to show positive changes: heart function improved and muscle strength increased. According to experts, similar processes occur with age in the human body: over the years, more cells with damaged mitochondria, including T-lymphocytes, accumulate. Energy deficiency in immunocytes leads, on the one hand, to a weakening of the defense against foreign agents, and on the other hand, to the development of chronic inflammation in the body.

Among the factors helping manage chronic inflammation, physical activity plays a crucial role. A group of biomedical engineers from Duke University found that exercise can prevent inflammation within muscle tissue⁸⁵. Scientists "grew" an artificial muscle platform, a cell culture capable of natural physiological contraction. The researchers then added gamma interferon, one of the proteins involved in inflammation and associated with various diseases that cause muscle atrophy and dysfunction, to these cells and simulated a chronic inflammatory process within the muscle tissue. This led to the loss of muscle mass and muscle strength.

In the next stage of the experiment, a pair of electrodes were connected to the artificial muscle to simulate physical activity. It turned out that muscle contractions lead to a decrease in the activity of inflammation. The technique's effectiveness was comparable to the effect of prescribing anti-inflammatory drugs.

Experts concluded that during exercise, muscles can counteract chronic inflammation by reducing its damaging effects.

ACQUIRED IMMUNITY – TARGETED ERADICATION

The main characteristic of acquired (adaptive) immunity is its high specificity – the ability to remember specific aggressors that pose a threat to health, and to eradicate them precisely when they meet again.

Two types of immune cells, B-lymphocytes, and T-lymphocytes, are responsible for the work of acquired immunity. B-lymphocytes are formed in the bone marrow and their immune activity is associated with the formation of antibodies – special proteins that are produced when they encounter a foreign agent called an antigen. Antibodies are a kind of body's "immune map": by their composition, we can learn about all encounters with foreign agents throughout life.

T-lymphocytes are several types of immune cells (T killers, T helpers, regulatory T cells) that are involved in recognizing aggressors, can destroy the pathogens themselves and infected and damaged cells, and regulate the immune system. T cells are "trained" in the thymus (thymus gland), the organ that plays the most important role in the immune system, and age-related changes in the thymus affect the rate of biological aging.

FUN FACT

THE IMMUNE AGE OF LONG-LIVERS IS 40 YEARS BEHIND THEIR BIOLOGICAL AGE

Researchers from the Buck Institute and Stanford University have identified several indicators helping to assess the immune age. The most informative biomarker of immune aging was the CXCL9 protein: it is known as a signal molecule that attracts immune cells to the site of infection. But a new study shows that CXCL9 also activates several genes that trigger inflammation and is involved in vascular and cardiac aging. Experiments on mice showed that suppression of this protein formation leads to the rejuvenation of vascular walls. Using a new tool, scientists assessed the immune clock rate in 902 people, among whom were healthy elderly people. It turned out that the immune age of long livers was on average 40 years behind their real age. Experts report a 105-year-old participant whose immunity indicators were consistent with a 25-year-old.

Experts also tested the new method in a group of 97 completely healthy people aged 25 to 97 years. It turned out that the level of the "aging protein" CXCL9 correlates with vascular wall stiffness (one of the key signs of cardiovascular aging).

THYMUS GLAND AND AGING

The older a person gets, the higher their risk of dying from cancer or even a common cold. One reason is age-related changes in the thymus⁸⁶ (thymus gland). This immune organ plays an essential role in preserving life by blocking the development of dangerous mutations and destroying dangerous microbes. However, as we age, the gland cells of the thymus are replaced by adipose tissue, and organ function declines. Therefore, one of the most important tasks of modern medicine is to find measures to rejuvenate the thymus gland and restore its protective functions.

As thymus function declines, the number of T lymphocytes capable of learning (recognizing foreign aggressors), decreases.

Researchers from the University of Copenhagen have published the results of a large-scale study, in which they traced the connection between a decrease in the level of lymphocytes in the blood (lymphopenia) and the risk of death from all causes⁸⁷.

The study involved more than 108,000 people between the ages of 20 and 100 (the average age is 68), which were followed for 12 years (2003–2015). 10,372 people died during this period. It turned out that people with lymphopenia had 1.6 times increased risk of dying from all causes, and mortality from heart disease, cancer, and respiratory infections was 2.8 times higher than in subjects with normal lymphocyte levels.

Experts explain this by the fact that a decrease in the number of lymphocytes indicates a reduced immunity readiness to respond to invading factors, leading to disease and death. Characteristically, lymphopenia develops with age in most people. It is associated with a decline in thymus function. Restoring the thymus gland potential will help manage many age-related problems, prevent cancer development, and probability of death from infections.

IS IT POSSIBLE TO TRANSPLANT THE THYMUS GLAND?

Transplantation of the thymus gland or its fragments to an adult could solve the problem of age-related decline in thymus function. It is possible, but to date, thymus transplants have only been performed on infants. Scientists from the Institute of Child Health (UK) 2017 published a paper on the results of thymus transplantation in children with Di George's syndrome, a genetic disease in which the thymus gland does not develop and there is a pronounced deficit of T lymphocytes⁸⁸.

Between 2009 and 2014, 12 children were transplanted, with an average age of 10 months. Immunosuppressive therapy was performed to suppress the reject phenomena. One patient had a rejection of a donor organ and underwent a second thymus transplant. Three patients died (two weeks, eight months, and two years after transplantation) from infectious complications caused by immunodeficiency.

9 of the 12 operated, at the time of publishing, were alive. Five to six months after transplantation, the recipients start to show their T lymphocytes, indicating the proper functioning of the transplanted organ. As a result, eight patients were taken off permanent antibiotic treatment, and five patients no longer needed supportive immunoreplacement drugs.

Doctors concluded that thymus transplantation is a method that allows us to establish the production of our T lymphocytes, but the chance of autoimmune reactions is still quite high.

Perhaps, as this practice improves, it will be possible to raise the issue of thymus transplantation not only for newborn children but also for elderly people with age-related decline of thymus gland function.

FUN FACT

"COCKTAIL" FOR THYMUS RECOVERY LED TO LIFE PROLONGATION

Experts from Stanford University, working on a medicine restoring the thymus gland, created the "elixir of life." Studies have shown that a cocktail of several substances "moved" the epigenetic clock back, giving subjects 2.5 additional years of life.

The initial objective of the study, which involved nine men between the ages of 52 and 65, was to stimulate the multiplication of active immune cells in the thymus gland. Previous studies have shown that injecting somatotropin (growth hormone) into the body helps reverse age-related changes in the thymus gland, but simultaneously with the positive effect it provokes diabetes.

In a new experiment, scientists decided to use a cocktail that included, in addition to growth hormone, substances that prevent diabetes development: metformin⁸⁹ and dehydroepiandrosterone⁹⁰. Specialists were able to achieve the desired result – the replacement of fat cells of the thymus with immune cells, avoiding diabetes development.

It turned out that the cocktail not only "strengthened" immunity, but also rejuvenated the body.

Specialists learned this by analyzing methyl tags that appear on the surface of DNA sites as they age, indicating a change in genomic activity. The cocktail of growth hormone and antidiabetic medications helped move the "hands of the epigenetic clock" by 2.5 years, and this effect was maintained in participants six months after the study.

It is not necessary to transplant the whole thymus – the donor gland scaffold can be enough⁹¹.

American scientists have found that one of the causes of age-related involution of the thymus gland is a microenvironment change. As a result, stem progenitor cells stop transforming into mature T lymphocytes. The proposed method consists in creating a new organ scaffold with a microenvironment suitable for lymphocyte multiplication.

The experiment was performed on mice: thymus was removed from donor animals and decellularized (cells were removed by freezing and thawing cycles followed by washing). As a result, a connective scaffold was left, which was transplanted to recipient mice with the thymus removed. The creation of an extracellular 3D matrix helped to form conditions for the transformation of stem progenitor cells into full-fledged T lymphocytes.

The study showed that the use of bioengineering technologies, helping to restore the proper cell microenvironment, contributes to thymus function restoration and can be used to rejuvenate the gland. Perhaps after the completion of preclinical trials conducted on laboratory animals, scientists will be able to perform thymus scaffold transplantation for humans as well.

EXERCISE AND NUTRITIONAL SUPPLEMENTS CAN IMPROVE THYMUS FUNCTION

The experiment conducted by specialists from the University of Birmingham (UK) showed that to rejuvenate the thymus, we need to move more⁹². A total of 125 amateur cyclists participated in the experiment: 75 between the ages of 55 and 79 and 55 between the ages of 20 and 36.

Subjects participated in a 100-kilometer race in 6.5 hours for men and a 50-kilometer race in 5.5 hours for women. In preparation for the competition, they trained regularly. The comparison group was people of similar age who are not into sports. Studies have shown that regular exercise helps the thymus of older people to remain as active as it was when they were young: the number of T lymphocytes in the "young" and "old" groups was almost identical.

A gentle method of thymus restoration was also proposed by scientists from the Singapore Immunology Network⁹³. Experts found that the formation of T killer cells in the thymus, the "first line of defense" cells during the invasion of foreign agents, is activated under the influence of lipid molecules. These fat molecules are produced by pathogenic bacteria and are synthesized in the thymus itself.

Scientists managed to decipher the structure of these signal substances and artificially synthesize their analogs. It turned out that administration of these molecules into the body leads to increased formation of T killers, which can be used to fight against infectious diseases, especially in people with a reduced thymus gland function due to age.

In Chinese medicine, there is a practice aimed at stimulating the immune system – thymus massage ("happiness point" massage). To find the "happiness point," you need to feel the sensitive area on the breastbone, located two fingers (about 2 centimeters) below the sternal notch (notch between collar bones). Affect "happiness point" with massage: nine times to one side and nine times to the other. Another way to affect is percussion – tapping the "happiness point." The frequency and intensity do not matter: what is important is that it does not cause discomfort. It is believed that these practices increase blood supply to the thymus gland, which is beneficial for thymus function.

Among the methods of alternative medicine aimed at rejuvenating the thymus is the chanting of mantras. It is believed that sound vibration occurring during the chanting of the Om mantra enhances blood flow to the thymus gland and helps to improve its function.

CONCLUSION: HOW TO MAINTAIN IMMUNITY?

Today we see the development of high technology, which with high probability will help soon to solve problems of age imbalance of the immune system, to slow down or to prevent the development of diseases associated with the aging of the body's defenses. However, even today we can support our immune system with a healthy lifestyle.

Good sleep is an important condition for the full functioning of the immune system. A study conducted at the University of Tübingen (Germany) showed that during sleep, T lymphocytes are "reprogrammed" and start to fight infection more actively⁹⁴. Scientists from the University of Texas Southwestern Medical Center (USA) and their colleagues from Australia found in a series of experiments that muscle exercise not only strengthens bones but also activates the formation of stem cells – lymphocyte precursors in the bone marrow, which affects the immune system⁹⁵.

However, it's important to understand that it's not just working on the physical aspects of our lifestyle, such as nutrition, movement, and sleep, important for maintaining a fully functioning immune system. Taking care of mental well-being also has a powerful effect on the body's defenses: techniques such as meditation, mindfulness, and relaxation will have a positive effect on immune function.

Thus, it is an integrated approach considering both the physical aspects of a healthy lifestyle and methods that promote stress resistance, as well as social interactions, that help to maintain the correct immune balance in the body, allowing you to stay young and healthy for a long time.

CHAPTER 9
METABOLISM

METABOLISM – THIS CONCEPT IS PORTRAYED WITH MANY MYTHS, WHICH SPREAD ACROSS THE GLOBAL NETWORK AT THE SPEED OF LIGHT. IN MOST PUBLICATIONS AND VIDEOS, "FAST METABOLISM" IS DECLARED A PREREQUISITE FOR STAYING SLIM AND YOUNG.

"Ten ways to boost your metabolism without dieting," "Lifehacks to increase your metabolic rate," "Top 10 foods to speed up your metabolism" – the Internet is full of such headlines. Various types of exercise, diets, supplements, teas, exposure to cold or heat, etc. are presented as levers to control the metabolism.

At the same time, there are also adepts of "slow metabolism," who consider the metabolism as something like a battery: the more actively it is used, the faster the charge runs out and the inevitable end comes. So, which is better for our metabolism – burn bright or just barely glow? How can we affect the speed of our metabolic processes, and what it will bring?

WHAT IS METABOLISM?

Every cell in our body needs energy to function properly, which comes with food. Energy release occurs during a huge number of chemical reactions involving the processes of the breakdown of molecules (catabolism) and the synthesis of new substances (anabolism). The totality of all these processes is called metabolism.

What body functions use the energy produced and in what quantity?

● Life processes support. There is an indicator called basal metabolism, which is the energy needed to sustain the body's vital functions. It is consumed to provide the processes of breathing, heartbeat, digestion, maintaining body temperature, regulation of the nervous and hormonal systems, tissue repair, and much more. All these processes take place every second of our lives, both during periods of activity and during sleep. Basal metabolism takes the lion's share of energy produced, 60 % to 75 % of calories that enter the body with food. At the same time, with age, the basal metabolic rate decreases by an average of 12 % every decade after a person reaches the age of 20⁹⁶. Scientists attribute this to a decrease in muscle mass, whose cells consume more energy even at rest, and an increase in the adipose tissue percentage, which is more inert in energy expenditure. It is generally believed that it is difficult to influence basal metabolism with any measures. It is also known that the rate of basal metabolism in men is 10 % higher than in women: males with normal build burn an average of 1 kcal/hour for each kilogram of body weight, while women burn 0.9 kcal/hour⁹⁷.

● Energy expenditure in digestion. The digestion itself requires energy: it is necessary to break down the food in the gastrointestinal tract, absorb the obtained molecules into the blood, and deliver them to the place of use or storage. Energy expenditure for digestion is called diet-induced thermogenesis and accounts for 5-10 % of calories consumed. However, different types of food take different amounts of energy to digest. For example, the rate of diet-induced thermogenesis for porridge based on various kinds of cereal (millet, oats, buckwheat) is about 18–19 %, for cottage cheese – 30–31 %, for butter – 1415 % of the caloric value of food products themselves⁹⁸. It was found that immediately after a meal the basal metabolism level increases, and the amount of energy absorbed also depends on the chemical composition of food: consumption of proteins increases the basal metabolic rate by 30–40 %, fats by 4-14 %, carbs by 4–7 %. This means that a person whose diet is dominated by protein products (cottage cheese, meat, etc.) will burn more energy per day than a person who eats a lot of fats and carbs⁹⁹.

● Total metabolism is the energy a person expends on physical and mental activity. Separately distinguish energy expenditures for daily physical activity: going to work, to the store, cleaning, cooking, etc., and the energy expenditures for special physical activity: sports, walking, and hard work that is not part of daily activity. Mental work also makes the body expend energy: the brain is a very energy-consuming organ, and with intense mental activity it can absorb up to one-third of the body's energy.

● Facultative thermogenesis – energy expenditure in stressful situations is isolated as a separate category. For example, with hypothermia, heat-regulating centers in the brain cause the body to expend more heat to maintain optimal body temperature.

IS IT POSSIBLE TO SPEED UP THE METABOLISM?

Searching for recommendations to speed up the metabolism is associated primarily with the desire to get rid of excess weight, with an attempt to shift metabolic processes towards the burning of ingested energy and to create a calorie deficit. However, if we consider the components of our metabolism, it becomes obvious that most of the energy during the day is spent on basal metabolism, i.e., on vital processes. This energy is spent no matter what kind of lifestyle we lead – devoting most of our time to physical and mental activity or lying passively on the couch.

Thus, the basic "energy capital" that can be disposed of in one way, or another is the calories we spend on total metabolism, that is, on physical and mental activity. The amount of energy expended for total metabolism is 30–40 % of the total amount of kilocalories consumed in metabolic processes. Therefore, one of the key recommendations for people who want to speed up their metabolism and lose weight is to lead a more active lifestyle. The importance of exercise in activating metabolic processes has been shown in several studies.

Physical activity is known to improve metabolic processes in the body, helping to convert food into energy and eliminate "waste." Substances formed during digestion, are called metabolites, which can be used to track how a person's metabolic profile changes in response to exercise.

Researchers from Australia measured about 200 metabolites in the blood of 52 soldiers before and after an 80-day program of weight and aerobic exercise and associated them with changes in fitness¹⁰⁰. It turned out that physical activity significantly changed the composition of metabolites in the soldiers' bodies: exercised muscles used much more "fuel" (e.g., fat), than before. They also recorded major changes in intestinal processes, in factors related to blood clotting, protein breakdown, and vasodilation to improve blood flow.

Therefore, scientists have concluded that exercise is the key to speeding up the metabolism in addition to having positive effects on blood pressure, heart rate, body weight, and fitness. The study confirms the central role of physical activity in the prevention of cardiovascular disease.

NEW INSIGHTS INTO THE METABOLISM (WHY DOESN'T MOVEMENT ALWAYS HELP?)

As some studies show, the principle of "eat less, move more" does not always lead to desired results – increased metabolism and weight loss. This paradigm was questioned in a study conducted by Herman Pontzer, professor of evolutionary anthropology at Duke University¹⁰¹.

For 10 years, Pontzer and his colleagues analyzed the metabolism of U.S. and European residents: they focused on both professional athletes, whose lifestyle is accompanied by significant energy expenditure, and office workers, who consume minimal calories for physical activity.

At the same time, experts were studying the characteristics of metabolic processes and energy expenditures among the members of the Hadza tribe. These are the inhabitants of Tanzania who led a "primitive" way of life, engage in hunting and gathering, and do not have access to such fruits of civilization as water supply and electricity.

It is logical to assume that tribal members, who walk at least 16,000 steps every day in search of food, expend significantly more energy than office workers who suffer from physical inactivity. However, Professor Pontzer's and his colleagues' research appeared to show otherwise. Scientists found that despite their high activity levels, the Hadza do not burn more energy per day than sedentary people in the U.S. and Europe.

According to scientists, this and other studies change views on the relationship between energy expenditure, physical activity, and diet. The study authors state that our metabolism is much more complex than it seems, and our actual energy expenditure cannot be measured by calculating the difference between "eaten" and expended calories.

"Our metabolic engines were not crafted by millions of years of evolution to guarantee a beach-ready bikini body," Herman Pontzer says. But rather, our metabolism has been primed "to pack on more fat than any other ape." What is more, our metabolism responds to changes in exercise and diet in ways that thwart our efforts to shed pounds."

At the same time, as the study authors claim, despite the equal energy expenditures of office workers and Tanzanian hunter-gatherers, the daily activity provides the members of the Hadza tribe with great bonuses. First, it's about strong health even in old age: at 60 and 70, the Hadza people rarely experience cardiovascular diseases, diabetes, obesity, hypertension, or osteoporosis.

"All those adjustments our bodies make responding to exercise are important for our health," emphasizes Professor Pontzer. "When we burn more calories on exercise, our bodies spend less energy on inflammation, stress reactivity (like cortisol), and other things that make us sick."

According to Pontzer and his colleagues, it is important for modern individuals living in industrialized countries to be active to keep up healthy. However, we should not rely too much on exercise to make our bodies burn calories more intensively in combating obesity. This new understanding of metabolism helps to realize that the body quickly adapts to additional physical activity by starting to burn energy in a more "narrow range."

Scientists from Baylor University (USA) obtained similar results in a study examining the energy expenditure patterns of children from Ecuador.¹⁰² The young subjects (they were from 5 to 12 years old when the study began) lived with their families in the Amazon rainforest. Like members of the Hadza tribe, they had no access to modern technology to make life easier, and they were subsistence farmers, devoting their time to hunting, fishing, gathering, and gardening. Experts analyzed not only the level of energy consumption of children from Ecuador but also used modern technology to understand exactly what the experiment participants spent their calories on during the day.

It turned out that the total energy expenditure of the young subjects did not differ from the energy expenditure of their peers from industrialized countries, although children from South America were more active (by at least 25 %) than children from the USA. At the same time, the basal metabolic rate (the amount of energy to support basic needs) of children from Ecuador was 20 % higher than that of their "civilized" peers, while their physical activity, in contrast, took less energy than that of the much less mobile children from North America.

Scientists found that the excess energy of basal metabolism in young inhabitants of the Amazon was spent on maintaining the tone of the immune system: children were less susceptible to colds and almost did not suffer from obesity, unlike their peers from the United States. Experts believe that despite similar daily energy consumption in both study groups, children from the United States are much more likely to be obese and to have a significantly higher risk of developing heart disease, diabetes, and other diseases than their peers from Ecuador.

This study updated the data obtained by Professor Pontzer and showed that children's metabolism has the same flexibility as adults' metabolic processes and can adjust to different levels of activity, including energy-saving mode.

Today, several studies show that physical activity plays an essential role in maintaining health, but it has a very limited efficiency potential when it comes to weight loss. The fight against obesity should be based primarily on reducing caloric intake. However, does a calorie deficit help to speed up metabolism? On the contrary! Studies show, that reducing the amount of dietary energy often leads to a slower metabolism. This point lies behind experiments about the effect of metabolic rate on longevity.

METABOLIC RATE AND LIFE EXPECTANCY

"Vital energy is like motor fuel, the faster the car goes, the faster the gas runs out" – this point of view is shared by supporters of the theories connecting the rate of metabolic processes and life expectancy. The origins of this position are in studies of the German physiologist Max Rubner, who in the early XX century proposed the rate of living theory. Rubner noted that the larger an animal and the longer it lives, the less energy it consumes per gram of body weight. Roland Prinzinger, a follower, and compatriot of Max Rubner, believes that all living creatures use around 2.5 million kJ per gram of body weight during their lifetime. According to Prinzinger, this is the "fuel volume" limiting our life.

In the early 21st century, German doctors Peter Axt and Michaela Axt-Gadermann wrote a popular science book called "The Joy of Laziness: Why Life Is Better Slower – and How to Get There". The authors claim that excessively active people (especially professional athletes) have a shorter life span, and suffer from heart and vascular diseases and cancer more often than those who do not show excessive activity.

At the same time, over the years with the advent of the rate of living theory, there have been many studies that refute Max Rubner's position, which linked the body size of an animal, its metabolic rate, and life expectancy. For example, a hummingbird is the smallest and most "metabolically active" of all birds: its heart rate in flight exceeds 1200 beats per minute, and its respiratory rate is 250. At such metabolic rates, a hummingbird's life span should be very short – no more than a year.

However, its average lifespan is about five years. It is comparable to the lifespan of most species of wild pigeons, having a much more "resting" metabolism and living 5–7 years. Moreover, there are some long-living hummingbirds, whose age makes 10–12 years.

One explanation that allows us to understand why such a huge energy consumption does not affect the lifespan of the hummingbird is related to daily fluctuations in the metabolic rates of this bird. During the night, the hummingbird's body temperature drops below 20 ℃ and the pulse rate drops to 50–100 bpm. The high-speed daytime metabolism is replaced by a nighttime anabiosis, similar to a short winter sleep.

The hummingbird example shows that Rubner and his followers' approach is too "mechanistic." Many factors affect the body's work, including metabolic processes, which are highly variable and adaptable to different conditions. At the same time, there is some common sense in longevity theory and similar hypotheses: during the last few decades, much research has been conducted to study the effect of various factors on metabolism (and longevity). These include caloric deficiency, hypoxia (oxygen deficiency), and heat deficiency.

HOW DOES CALORIE RESTRICTION AFFECT METABOLISM AND LIFE EXPECTANCY?

Scientists believe that one of the secrets to the longevity of Okinawans is a reduced-calorie diet. Inhabitants of this blue-zone region have incredible longevity, with many crossing the 100-year threshold. In addition, Okinawans are much less likely than other Japanese to die from cardiovascular disease (59 %) and cancer (69 %)¹⁰³. By analyzing the diet of Okinawans, scientists concluded that school students in the region consume 38 % fewer calories than their peers in other regions of Japan, and the caloric content of the daily food diet of adult Okinawans is on average 20 % lower than that of other inhabitants of the Land of the Rising Sun.

Yet, the link between the low-calorie diet of Okinawans and their high life expectancy (as well as their excellent health in adulthood) is still only a hypothesis. Scientists continue to actively investigate it, conducting various experiments involving animals and humans.

Experts from Texas University studied the metabolism of a group of mice whose calorie intake was 40 % lower than that of animals in the control group from the age of 6 months until the end of their lives¹⁰⁴. These rodents showed a decrease in metabolic rate at 6–12 months of age. However, when the mice reached 18 months of age, their metabolism activity became the same as that of animals on a standard calorie intake.

Scientists concluded that a calorie deficit leads to a gradual shift in metabolism and the activation of adaptive mechanisms that normalize the rate of metabolic processes. According to experts, it is the mobilization of compensatory systems similar to those activated during mild stress that may underlie the increase in lifespan with a low-calorie diet.

Meta-analysis of studies on the connection between metabolic rates, caloric deficit, and longevity of animals showed that there is no direct and obvious relationship between these factors¹⁰⁵. As it turned out, there are many factors affecting the relationship between metabolic activity and longevity of animals, including housing conditions and individual experience.

The most significant experiment to study the effects of caloric restriction on metabolic processes in humans was conducted in 2018 as part of the Calerie (Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy) project¹⁰⁶. The experiment involved over 50 volunteers who reduced their caloric intake by 25 %; the subjects adhered to this restriction for two years. During the whole experiment, the subjects lost an average of 9.4 kilograms, and the main weight loss was due to a decrease in body fat. After a period of active weight loss, there was a period of stabilization (maintenance of the achieved results).

During the period of active weight loss, a 10 % slowdown of basal metabolism (energy expenditure during sleep) was observed in the subjects. A study of the hormonal profile of the subjects showed that the level of leptin decreased in the blood of the volunteers, indicating a slower metabolism. Also, during the period of active weight loss, there was an increase in adiponectin, a hormone synthesized by fat cells (its level decreases in obesity). Adiponectin is a regulator of metabolic processes, and its increase indicates a tendency to normalization of metabolism. During the period of weight stabilization, there was a decrease in thyroid hormones in the volunteers, which indicated a slowdown in the rate of metabolic processes in the body. A low concentration of these hormones is recognized as one of the biomarkers of aging.

The experiment showed that changes occurring against a background of prolonged caloric deficiency in the human body cannot be interpreted as unambiguously positive. On the one hand, in active weight loss, there are positive transformations, associated with a decrease in leptin and adiponectin. On the other hand, during prolonged caloric restriction, there are also bad shifts, which include a decrease in thyroid hormone levels.

LOWERING BODY TEMPERATURE AND AN INCREASE IN LIFE EXPECTANCY

Man is a warm-blooded animal. The ability to regulate body temperature makes it possible to live in regions with different climates and to maintain a high level of activity year-round. But this evolutionary bonus is paid for, for example, by huge energy expenditures, due to which warm-blooded animals consume dozens of times more food than cold-blooded creatures of the same weight, as well as, quite probably, the ability to live long.

Almost all animals with the ability to slow down metabolism, including temporary "cooling" during hibernation (or torpor), live longer than evolutionarily related species that maintain a high body temperature. For example, mice that are awake year-round rarely live beyond four years, while the lifespan of gophers, representatives of the same order that go into hibernation, is about seven years.

According to biologists, the ability to lower body temperature by 2–3 degrees helps increase lifespan by 1.5–2 times.

The only mammal known to science whose body temperature depends on its environment is the naked mole rat. This creature living in savannas and semideserts of some African regions is a close relative of mice and rats but lives ten times longer than its closest relatives: about 30 years against 1.5–3 years typical for ordinary rodents.

Naked mole rats live in colonies in underground tunnels: when it gets cooler, they move closer to the surface and gather in groups, minimizing heat loss. The animals are resistant to oxygen deficiency and high concentrations of carbon dioxide, which are fatal for other rodents. Researchers believe that the reason for this persistence is the slow metabolism, which is half as fast as that of similar individuals. The low body temperature, along with some other features of mole rats (for example, the ability to get "stuck" in childhood for their whole life), scientists believe to be the key factor in their unprecedented lifespan for rodents.

FUN FACT

CAN A PERSON GO INTO HIBERNATION?

Getting a person into the so-called hibernation state – a process in which the metabolic rate, namely heart rate, respiration, body temperature, oxygen level, etc., is reduced – is a plot for a science fiction movie, because only some animals can hibernate, but not humans. However, studies have shown that artificial activation of certain neurons allows mice to go into a state similar to hibernation – torpor – even though it is not natural for them. And if it was possible for them, it may be possible for humans as well. The uses of the method range from treating a multitude of diseases to space travel.

Is it possible to artificially lower body temperature to increase life expectancy? Experts from Scripps Research in California (USA) found that the health effect of low-calorie diets is related to metabolic processes that cause a decrease in body temperature¹⁰⁷. They took two groups of mice, which were placed in cells with different temperatures: the first was 22 ℃ (normal room temperature), the second – 30 ℃ (at this temperature the body of mice is in heat balance with the environment, and the mechanisms of body thermoregulation are inactive).

Then they were divided into subgroups: some of them gradually reduced the amount of food per day, and others ate as usual. During the experiment, scientists monitored the changes in metabolites in the blood and brain of the animals, depending on their diet or body temperature. The study found that under conditions of caloric restriction, the temperature had the same or even greater effect on metabolism than the amount of nutrients.

The analysis identified specific metabolites responsible for changes in body temperature. For example, the hypothalamus of mice living at room temperature produced large amounts of nitric oxide molecules and the neuropeptide leucine-enkephalin. Scientists separately injected these metabolites into mice and found that the health effect of caloric restriction increased.

OXYGEN DEFICIENCY, METABOLISM, AND LONGEVITY

One of the secrets of the naked mole rats' long life, scientists believe, living in hypoxia – oxygen deficiency. At present, scientists conduct research to study the effect of artificially created hypoxic conditions on health and longevity. The most spectacular experiment in this direction was conducted on animals. Scientists from the National Academy of Medical Sciences of Ukraine and the Ben-Gurion University of the Negev, using artificial hypoxia, managed to turn ordinary mice into their long-lived brethren – naked mole rats¹⁰⁸.

Experts have simulated the living conditions of naked mole rats in cages for mice: to do this, they have reduced the oxygen content from 20 to 10 % and increased the concentration of carbon dioxide from a small fraction of the % to up to 10 %. Next, the experts made three groups of mice live in these stuffy conditions: young, adult, and elderly – for three months. It turned out that during this time the number of respirations was halved in rodents of all groups, and body temperature dropped by several degrees and then stabilized at this level.

The animals began to eat 40–50 % less than usual (although they had plenty of food) and lost 25–30 % weight. In addition, the scientists recorded that the rodents were not stressed – this was shown by experiments at the intracellular level. In terms of behavior, the animals also showed no changes: their activity and sleep remained at the same level. Specialists noted that the wounds on the mice healed faster than under normal conditions. That is, under the heat, the laboratory mice became like naked mole rats.

According to scientists, the body's adaptation to low oxygen levels is one of the reasons for the longevity of mountain dwellers. Scientists from the University of New Mexico (USA) and Fudan University (China) found out that the representatives of the Mosuo people, who live in high-mountain areas of the Himalayas, suffer from hypertension much less often than the inhabitants of plains and foothills¹⁰⁹. Moreover, they practically do not develop anemia, which is characteristic of diabetes (although cases of diabetes are registered). Experts found that highlanders do not suffer from oxygen hunger even in situations when the oxygen concentration in the air significantly decreases: in response to this, the blood vessels of highlanders can expand as much as possible. This way the body prevents the development of hypoxia.

CONCLUSION: SHOULD WE CONSCIOUSLY AFFECT THE METABOLIC RATE?

Research shows that our metabolism is a very complex system with multilevel regulation. Therefore, it is hard to affect it with simple methods (e.g., moving more and eating less). Thousands of years of evolutionary development have taught our metabolic mechanisms to hold their own when faced with factors such as hunger or excessive activity because the body perceives them as a threat to survival. At the same time, measures that are usually recommended to speed up the metabolism, especially physical activity, have a powerful positive effect on the body, protecting it from the development of a wide range of diseases.

Following calorie deficit dietary recommendations also leads to positive changes. Restricting energy intake from food helps control weight and acts as a "soft" stressor, activating the body's adaptation mechanisms to increase longevity. Our task is not so much to find levers to speed up or slow down the metabolism, but to find the optimal balance between energy storage and expenditure, between the state of tension and relaxation, and between excessive and "useful" stress. A lifestyle of sufficient physical activity, a rational diet, practices that allow us to cope with excessive stress and healthy sleep will create the conditions for maintaining the rate of metabolic processes that is necessary to stay healthy for many years.

CHAPTER 10
NUTRITION

HUMAN HEALTH DEPENDS NOT ONLY ON GENETIC FACTORS BUT IS LARGELY DETERMINED BY HABITS, LIFESTYLE, AND ECOLOGY. NUTRITION PLAYS THE MOST IMPORTANT ROLE IN MAINTAINING A HEALTHY BODY: IT IS ABOUT THE AMOUNT OF FOOD CONSUMED, ITS QUALITY, AND THE RATIO OF DIFFERENT COMPONENTS IN THE DIET.

Many diseases that have become widespread around the world in recent decades are related to imbalances in nutrition. Therefore, everyone needs to know the basic principles of a healthy diet, as well as consider the individual characteristics and needs of the body.

INTRODUCTION TO NUTRITIOLOGY

The diet of many modern people is quite monotonous and includes many high-calorie dishes, fats, and simple carbohydrates, provoking the development of metabolic disorders and obesity. At the same time, the modern style of the diet of people in developed countries is characterized by a low content of foods rich in fiber and vitamins, healthy fats, and high-quality proteins.

For this reason, the number of people suffering from the consequences of poor nutrition is increasing day by day. First, we are talking about a global obesity epidemic. According to statistics from the World Health Organization, at least 2.8 million people die annually from diseases associated with excess weight, and experts from the Endocrine Society of the USA report that obesity is the cause of death of over 4 million people a year. At the same time, the number of people suffering from overweight is increasing every day. Among other diseases caused by irrational nutrition – are atherosclerosis, coronary heart disease, diabetes, osteoporosis, hypertension, and many other pathologies.

There is a whole science that studies how the different components in food interact with each other and the body. It is called nutritiously: the name comes from the Latin word nutritio – "nutrition," and the Greek word λόγος – "study." Nutrition experts are interested in the nuances of people's eating behavior, such as the motivations that guide people's food choices, the development of both global healthy eating strategies, and individual dietary recommendations.

The main task of nutrition is to provide the body with nutrients. They serve as sources of energy and act as a building material for the creation of cells and intracellular structures, hormones, enzymes, and other biologically active molecules, for tissue renewal. Protein, fat, and carbohydrate molecules in food are macronutrients and are the basic building and energy substrates.

Unlike macronutrients, which shall be consumed normally each day, micronutrients are only needed in very small amounts. Micronutrients include vitamins and minerals. For example, they are used to regulate metabolic processes, affect the speed of biochemical reactions, and some are part of larger molecules. A deficiency of proteins, fats, and carbohydrates quickly leads to tangible consequences: a person suffers from a lack of energy, metabolic disorders, and general exhaustion. It takes time to feel the effects of micronutrient deficiencies, but the negative consequences are inevitable.

The important role that food plays in health and disease has been evident since ancient times: even Hippocrates mentioned in his manuscripts the connection between gout (a metabolic disease that affects joints and kidneys) and an excess of meat products in the diet. However, the position in which one or another macro or micronutrient is declared an enemy or panacea for all health problems is fundamentally wrong.

In the 1970s, scientists discovered that cholesterol plays an important role in the development of cardiovascular disease. This discovery led to a veritable "fat-free boom," as over the next two decades people began to cut back on fat in their meals, and fat-free foods filled stores. But further research showed that vegetable fats, as well as fatty fish, on the contrary, protect against atherosclerosis and heart disease.

The discovery of the effect of vitamins in maintaining health was the reason for their enormous popularity. However, there is still no evidence that synthetic vitamins can make a significant contribution to disease prevention. On the contrary, studies show that vitamin addiction can lead to health problems.

Today, the key criteria for a healthy diet are balanced (the presence of all micro and macronutrients in sufficient but not excessive amounts) and a personalized approach to dietary planning.

WHAT DOES GUT HEALTH DEPEND ON?

For many years, the functioning of the human digestive system was perceived from a mechanistic point of view. Digestion was seen as a step-by-step grinding of food – mechanically (in the oral cavity) and then chemically by enzymes. As a result, eaten food turns into the smallest structural components, which enter the blood and lymph through the intestinal wall, and the undigested remains are excreted with feces.

Today, however, it is becoming apparent that digestion is a complex process with multilevel regulation. It was found that there is a close connection between the brain and the digestive tract. The intestines are "equipped" with their nervous system (enteric nervous system, ENS), which can function independently of the central nervous system. The ENS consists of a huge number of nerve cells and is regulated by the same neurotransmitters that are needed for brain functioning, such as serotonin and dopamine.

The brain and gut are constantly exchanging signals (the "gut-brain" axis). It is not surprising that the digestive tract is sensitive to stress and mood swings, and, on the contrary, eating a certain food allows it to affect our emotional state, to calm down or, to cheer up.

The digestive tract is filled with a huge number of microorganisms (there are 100,000 times more of them than people on Earth). Collectively, they are called the intestinal microbiota. Its representatives – bacteria, archaea, Proteus, fungi, and viruses – help to digest food, regulate metabolism, neutralize dangerous substances, and strengthen the immune system.

Microbiota composition is largely determined by nutrition style. In one study, Italian researchers from the University of Florence compared the microbiota of children living in rural settings in Burkina Faso, West Africa, with the microbiota of children living in urban settings in Florence¹¹⁰. The former ate mostly natural foods: their diet included cereals, vegetables, and sometimes chicken. The latter ate mostly pasta, pizza, chips, breakfast cereals, and soda. It turned out that the microbiota of children from Burkina Faso was richer and more diverse, and the level of beneficial bacteria was higher than that of the children from Florence. Poor and "unhealthy" intestinal microbiome of Western children formed from such a diet, according to many scientists, is a health hazard because it provokes allergic reactions, obesity, type 2 diabetes, autoimmune diseases, mental disorders, and many other diseases.

Low-carbohydrate, raw food diets, and other dietary fashion advocates often call for giving up certain foods in favor of others, eating less, and exercising a lot to reduce excess body weight. But the human digestive system is much more complex. Intestinal microorganisms determine exactly how appetite will be regulated, energy will be expended, how many calories will be deposited as fat, and how much inflammation will occur in cells. The intestinal microbial landscape is unique to each person, and its composition determines the individual characteristics of the assimilation of certain foods, and metabolic and mental processes.