The Power Of Youth. How To Tune Our Mind And Body For A Long And Healthy Life
Andrei Fomenko
During the last couple of decades, science and medicine have taken a great step toward understanding what aging is. Technologies of cell reprogramming, tissue regeneration, genetic engineering, young blood transfusion, and many others are developing right before our very eyes. But it is not only the development of hightech that is crucial because even the less obvious things–from the placebo effect and the way of thinking to visualization and even ASMR–can help to defeat aging. Everything you need to know about how to live a long life without the painful agony of old age is right in your hands. This book contains the most relevant scientific reports on how to slow down age-related changes and stay young as long as possible.
Such a diverse view on the problem of aging–in terms of genetics, physiology, psychology, evolution, quantum mechanics, mathematics, etc. – distinguishes this book from many papers devoted to the prolongation of life and youth.
Andrei Fomenko
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
Все права защищены. Данная электронная книга предназначена исключительно для частного использования в личных (некоммерческих) целях. Электронная книга, ее части, фрагменты и элементы, включая текст, изображения и иное, не подлежат копированию и любому другому использованию без разрешения правообладателя. В частности, запрещено такое использование, в результате которого электронная книга, ее часть, фрагмент или элемент станут доступными ограниченному или неопределенному кругу лиц, в том числе посредством сети интернет, независимо от того, будет предоставляться доступ за плату или безвозмездно.
Копирование, воспроизведение и иное использование электронной книги, ее частей, фрагментов и элементов, выходящее за пределы частного использования в личных (некоммерческих) целях, без согласия правообладателя является незаконным и влечет уголовную, административную и гражданскую ответственность.
© A. Fomenko, 2023
© Alpina PRO LLC, 2023
* * *
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 geroprotectors[1 - Geroprotectors is the name given to a group of certain substances or therapeutic methods that help to increase longevity. Read more: Fomenko A. N., Proshkina E. N., Fedintsev A. Yu., Tsvetkov V. O., Shaposhnikov M. V., Moskalev A. A. "Potential geroprotectors." – Ed. note.] 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 VSH25[2 - VSH25 is a project to prolong life and preserve health. Read more at vsh25.net. – Ed. note.] 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 accommodation[3 - Accommodation of the eye is its ability to focus on objects at different distances by changing the refractive properties of the lens. – Ed. note.] (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 processes[4 - López-Otín C., Blasco M. A., Partridge L., Serrano M., Kroemer G. The hallmarks of aging. Cell. 2013 Jun 6;153(6):1194-217. doi:10.1016/j.cell.2013.05.039. PMID: 23746838; PMCID: PMC3836174.].
● 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 aging[5 - Jin K. Modern Biological Theories of Aging. Aging Dis. 2010 Oct 1;1(2):72–74. PMID: 21132086; PMCID: PMC2995895.].
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) signaling[6 - Van Heemst D. Insulin, IGF-1 and longevity. Aging Dis. 2010 Oct;1(2):147-57. Epub 2010 Aug 26. PMID: 22396862; PMCID: PMC3295030.].
● 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 immunosenescence[7 - Immunosenescence begins at 5–7 years and completes by puberty, but small fragments of active glandular tissue persist throughout a human's life. – Ed. note.] – age-related changes in the thymus gland responsible for training immune cells[8 - Thomas R., Wang W., Su D. M. Contributions of Age-Related Thymic Involution to Immunosenescence and Inflammaging. Immun Ageing. 2020 Jan 20;17:2. doi:10.1186/s12979-020-0173-8. PMID: 31988649; PMCID: PMC6971920.].
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 - Freitas A. A., de Magalhães J. P. A review and appraisal of the DNA damage theory of aging. Mutat Res. 2011 Jul-Oct;728(1–2):12–22. doi:10.1016/j.mrrev.2011.05.001. Epub 2011 May 10. PMID: 21600302.].
● 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 cancer[10 - Yurov Y. B., Iourov I. Y., Monakhov V. V., Soloviev I. V., Vostrikov V. M., Vorsanova S. G. The variation of aneuploidy frequency in the developing and adult human brain revealed by an interphase FISH study. J Histochem Cytochem. 2005 Mar;53(3):385-90. doi:10.1369/jhc.4A6430.2005. PMID: 15750026.].
● 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 lipids[11 - Afanas'ev I. Signaling and Damaging Functions of Free Radicals in AgingFree Radical Theory, Hormesis, and TOR. Aging Dis. 2010 Oct;1(2):75–88. Epub 2010 Jul 12. PMID: 22396858; PMCID: PMC3295029.].
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 cells[12 - Warner H. R., Hodes R. J., Pocinki K. What does cell death have to do with aging? J Am Geriatr Soc. 1997 Sep;45(9):1140-6. doi:10.1111/j.15325415.1997.tb05981.x. PMID: 9288026.].
● Elevational (ontogenetic) theory of aging. In the mid-twentieth century, the Soviet gerontologist V. M. Dilman related aging and ontogeny[13 - Ontogeny is the individual development of an organism. – Ed. note.] (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 division[14 - Razgonova M. P., Zakharenko A. M., Golokhvast K. S., et al. Telomerase and telomeres in aging theory and chronographic aging theory (Review). Mol Med Rep. 2020;22(3):1679–1694. doi:10.3892/ mmr.2020.11274.]. 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 tissues[15 - Shay J. W., Wright W. E. Telomerase activity in human cancer. Curr Opin Oncol. 1996 Jan;8(1):66–71. doi:10.1097/00001622-199601000-00012. PMID: 8868103.].
● 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 II[16 - Furman D., Campisi J., Verdin E., et al. Chronic inflammation in the etiology of disease across the life span. Nat Med. 2019;25:1822–1832. doi:10.1038/s41591-019-0675-0.].
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 aging[17 - Gomes M. J., Martinez P. F., Pagan L. U., et al. Skeletal muscle aging: influence of oxidative stress and physical exercise. Oncotarget. 2017 Mar 21;8(12):20428-20440.doi:10.18632/oncotarget.14670. PMID: 28099900; PMCID: PMC5386774.], activates the antioxidant systems of the body[18 - Vargas-Mendoza N., Morales-González Á., Madrigal-Santillán E. O., et al. Antioxidant and Adaptative Response Mediated by Nrf2 during Physical Exercise. Antioxidants (Basel). 2019 Jun 25;8(6):196. doi:10.3390/antiox8060196. PMID: 31242588; PMCID: PMC6617290.], normalizes metabolic processes[19 - Brandao C. F. C., de Carvalho F. G., Souza A. O., et al. Physical training, UCP1 expression, mitochondrial density, and coupling in adipose tissue from women with obesity. Scand J Med Sci Sports. 2019 Nov;29(11):1699–1706. doi:10.1111/sms.13514. Epub 2019 Jul 22. PMID: 31282585.], stimulates the formation of somatotropic hormone (growth hormone), which significantly accelerates regeneration processes in the body[20 - Kanaley J. A. Growth hormone, arginine, and exercise. Curr Opin Clin Nutr Metab Care. 2008 Jan;11(1):50-4. doi:10.1097/MCO.0b013e-3282f2b0ad. PMID: 18090659.], helps normalize blood pressure levels and reduces the risk of hypertonia[21 - Lou M., Zong X. F., Wang L. L. Curative treatment of hypertension by physical exercise. Eur Rev Med Pharmacol Sci. 2017 Jul;21(14):3320–3326. PMID: 28770948.].
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 night[22 - Hirshkowitz M., Whiton K., Albert S. M., et al. National Sleep Foundation's sleep time duration recommendations: methodology and results summary. Sleep Health. 2015 Mar;1(1):40–43. doi:10.1016/j. sleh.2014.12.010. Epub 2015 Jan 8. PMID: 29073412.]. 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 years[23 - Kwak S., Kim H., Chey J., Youm Y. Feeling How Old I Am: Subjective Age Is Associated With Estimated Brain Age. Front Aging Neurosci. 2018;10:168. Published 2018 Jun 7. doi:10.3389/ fnagi.2018.00168.]. 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 scientists[24 - Stephan Y., Sutin A. R., Terracciano A. Subjective Age and Mortality in Three Longitudinal Samples. Psychosom Med. 2018 Sep;80(7):659–664. doi:10.1097/PSY.0000000000000613. PMID: 29864106; PMCID: PMC6345273.]. 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 animals[25 - Povedano J. M., Martinez P., Serrano R., et al. Therapeutic effects of telomerase in mice with pulmonary fibrosis induced by damage to the lungs and short telomeres. Elife. 2018;7:e31299. Published 2018 Jan 30. doi:10.7554/eLife.31299.]. 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 Denisovans[26 - Reich D., Green R., Kircher M., et al. Genetic history of an archaic hominin group from Denisova Cave in Siberia. Nature. 2010;468, 1053–1060. doi:0.1038/nature09710.].
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 planet[27 - Venter J. C., Remington K., Heidelberg J. F., et al. Environmental genome shotgun sequencing of the Sargasso Sea. Science. 2004 Apr 2;304(5667):66–74. doi:10.1126/science.1093857.]. 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 2005[28 - Fraga M. F., Ballestar E., Paz M. F., et al. Epigenetic differences arise during the lifetime of monozygotic twins. Proceedings of the National Academy of Sciences of the United States of America. 2005;102(30), 10604-10609. doi:10.1073/pnas.0500398102.]. 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 transformations[29 - Waterland R. A., Jirtle R. L. Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol Cell Biol. 2003;23(15):52935300. doi:10.1128/mcb.23.15.5293–5300.2003.]. 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 Francisco[30 - Ornish D., Magbanua M. J., Weidner G., et al. Changes in prostate gene expression in men undergoing an intensive nutrition and lifestyle intervention. Proceedings of the National Academy of Sciences of the United States of America. 2008;105(24), 8369–8374. doi:10.1073/ pnas.0803080105.]. 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 obesity[31 - Rönn T., Volkov P., Davegårdh C., et al. A six months exercise intervention influences the genome-wide DNA methylation pattern in human adipose tissue. PLoS Genet. 2013 Jun;9(6):e1003572. doi:10.1371/journal.pgen.1003572. Epub 2013 Jun 27. PMID: 23825961; PMCID: PMC3694844.].
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 gain[32 - Graff M., Scott R. A., Justice A. E., et al. Genome-wide physical activity interactions in adiposity – a meta-analysis of 200,452 adults. PLoS Genet. 2017;13(4):e1006528. doi:10.1371/journal.pgen. 1006528.]. 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 disorder[33 - Massachusetts General Hospital. (2019, November 5). Physical activity may protect against new episodes of depression. Science Daily. www.sciencedaily.com/releases/2019/11/191105113510.htm (http://www.sciencedaily.com/releases/2019/11/191105113510.htm).]. 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 smoked[34 - Joehanes R., Just A. C., Marioni R. E., et al. Epigenetic Signatures of Cigarette Smoking. Circ Cardiovasc Genet. 2016;9(5):436–447. doi:10.1161/CIRCGENETICS.116.001506.]. 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 tumors[35 - Garaycoechea J., Crossan G., Langevin F., et al. Alcohol and endogenous aldehydes damage chromosomes and mutate stem cells. Nature. 2018;553, 171–177. doi:10.1038/nature25154.]. 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 children[36 - Schrott R., Acharya K., Itchon-Ramos N., et al. Cannabis use is associated with potentially heritable widespread changes in autism candidate gene DLGAP2 DNA methylation in sperm. Epigenetics. 2020;15(1–2):161–173. doi:10.1080/15592294.2019.1656158.]. 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 mood[37 - Slotkin T. A., Skavicus S., Levin E. D., Seidler F. J. Paternal. 9-Tetrahydrocannabinol Exposure Prior to Mating Elicits Deficits in Cholinergic Synaptic Function in the Offspring. Toxicological Sciences. 2020 Apr;174(2), 210–217. doi:10.1093/toxsci/kfaa004.].
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 body[38 - Madaniyazi L., Li S., Li S., Guo Y. Candidate gene expression in response to low-level air pollution. Environ Int. 2020 Jul;140: 105610. doi:10.1016/j.envint.2020.105610. Epub 2020 Apr 2. PMID:32248990.]. 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 development[39 - Noniashvili E. M., Grudinina N. A., Kustova V. E., etc. DNA methylation in early mouse embryogenesis influenced by bisphenol A. Ecological genetics. 2017. 15 (3). P. 42–53.].
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 imprinting[40 - Anway M. D., Cupp A. S., Uzumcu M., Skinner M. K. Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science. 2005 Jun 3;308(5727):1466-9. doi:10.1126/science.1108190. Erratum in: Science. 2010 May 7;328(5979):690. PMID: 15933200.]. 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 activity[41 - Kiecolt-Glaser J. K., Loving T. J., Stowell J. R., et al. Hostile marital interactions, proinflammatory cytokine production, and wound healing. Arch Gen Psychiatry. 2005;62(12):1377–1384. doi:10.1001/ archpsyc.62.12.1377.]. 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 number[42 - Sender R., Fuchs S., Milo R. Revised Estimates for the Number of Human and Bacteria Cells in the Body. Published: August 19, 2016. doi:10.1371/journal.pbio.1002533.].
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 type[43 - Spalding K. L., Bhardwaj R. D., Buchholz B. A., Druid H., Frisén J. Retrospective Birth Dating of Cells in Humans. doi:10.1016/j. cell.2005.04.028PlumX Metrics.]. 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 years[44 - Kong S., Zhang Y. H., Zhang W. Regulation of Intestinal Epithelial Cells Properties and Functions by Amino Acids. doi:10.1155/2018/ 2819154.].
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 neurons[45 - Azevedo F. A. C., Carvalho L. R. B., Grinberg L. T., et al. Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled-up primate brain. Published: 18 February 2009 doi:10.1002/cne.21974.].
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 × 10
) atoms, 96.5 % of which are chemical elements[46 - Chemical element is a type of atom that has certain chemical properties. The adult body consists of more than 60 chemical elements – Ed. note.] such as hydrogen, oxygen, carbon, and nitrogen. About 4 % are other ones: calcium, phosphorus, sodium, potassium, sulfur, etc.[47 - Alberts B., Johnson A., Lewis J., et al. Molecular Biology of the Cell. 4th edition. The Chemical Components of a Cell. https://www.ncbi.nlm.nih.gov/books/NBK26883/#A166 (https://www.ncbi.nlm.nih.gov/books/NBK26883/#A166).].
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 brain[48 - Zaidi Z. F. Gender Differences in Human Brain: A Review. The Open Anatomy Journal. 2010;2:37–55. https://benthamopen.com/AB-STRACT/TOANATJ2-37.].
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 billion[49 - Von Bartheld C. S., Bahney J., Herculano-Houzel S. The search for true numbers of neurons and glial cells in the human brain: A review of 150 years of cell counting. J Comp Neurol. 2016;524(18):3865–3895. doi:10.1002/cne.24040.].
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 synapses[50 - Synapses are divided into chemical, electrical, and mixed. – Ed. note.]: 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 same[51 - Von Bartheld C. S., Bahney J., Herculano-Houzel S. The search for true numbers of neurons and glial cells in the human brain: A review of 150 years of cell counting. J Comp Neurol. 2016 Dec 15;524(18):3865–3895. doi:10.1002/cne.24040. Epub 2016 Jun 16. PMID: 27187682; PMCID: PMC5063692.].
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" axis[52 - The gut-brain axis includes the entire pool of intestinal microorganisms (microbiota), the "intestinal brain" and the central nervous system. – Ed. note.]. 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 disease[53 - Banks W. A., Reed M. J., Logsdon A. F., et al. Healthy aging and the blood-brain barrier. Nat Aging. 2021;1:243–254. doi:10.1038/s43587-02100043-5.].
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 impairment[54 - Tobin M. K., Musaraca K., Disouky A., Shetti A., Bheri A., Honer W. G., Kim N., Dawe R. J., Bennett D. A., Arfanakis K., Lazarov O. Human Hippocampal Neurogenesis Persists in Aged Adults and Alzheimer's Disease Patients. Cell Stem Cell. 2019 Jun 6;24(6):974–982.e3. doi:10.1016/j.stem.2019.05.003. Epub 2019 May 23. PMID: 31130513; PMCID: PMC6608595.].
Neurobiologists from the University of Jyväskylä (Finland) found during experiments in animals that prolonged aerobic exercise increases neurogenesis in the adult brain[55 - Nokia M. S., Lensu S., Ahtiainen J. P., Johansson P. P., Koch L. G., Britton S. L., Kainulainen H. Physical exercise increases adult hippocampal neurogenesis in male rats provided it is aerobic and sustained. J Physiol. 2016;594: 1855–1873. doi:10.1113/JP271552.]. 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 age[56 - Phillips C. Lifestyle Modulators of Neuroplasticity: How Physical Activity, Mental Engagement, and Diet Promote Cognitive Health during Aging. Neural Plast. 2017;2017:3589271. doi:10.1155/2017/3589271. Epub 2017 Jun 12. PMID: 28695017; PMCID: PMC5485368.]:
● 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 connections[57 - Dinoff A., Herrmann N., Swardfager W., et al. The Effect of Exercise Training on Resting Concentrations of Peripheral Brain-Derived Neurotrophic Factor (BDNF): A Meta-Analysis. PLOS One. 2016;11(9): e0163037. doi:10.1371/journal.pone.0163037.]. 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 brain[58 - Li P., Legault J., Litcofsky K. A. Neuroplasticity as a function of second language learning: anatomical changes in the human brain. Cortex. 2014 Sep;58:301-24. doi:10.1016/j.cortex.2014.05.001. Epub 2014 May 17. PMID: 24996640.]. 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 neuroplasticity[59 - Fox K. C., Nijeboer S., Dixon M. L., et al. Is meditation associated with altered brain structure? A systematic review and meta-analysis of morphometric neuroimaging in meditation practitioners. Neurosci Biobehav Rev. 2014 Jun;43:48–73. doi:10.1016/j.neubiorev.2014.03.016. Epub 2014 Apr 3. PMID: 24705269.]. 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 elderly[60 - Devore E. E., Kang J. H., Breteler M. M., Grodstein F. Dietary intakes of berries and flavonoids in relation to cognitive decline. Ann Neurol. 2012 Jul;72(1):135-43. doi:10.1002/ana.23594. Epub 2012 Apr 26. PMID: 22535616; PMCID: PMC3582325.]. 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 abilities[61 - Farzaei M. H., Rahimi R., Nikfar S., Abdollahi M. Effect of resveratrol on cognitive and memory performance and mood: A meta-analysis of 225 patients. Pharmacol Res. 2018 Feb;128:338–344. doi:10.1016/j. phrs.2017.08.009. Epub 2017 Aug 26. PMID: 28844841.].
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 factors[62 - Calder P. C. Omega-3 fatty acids and inflammatory processes: from molecules to man. Biochem Soc Trans. 2017 Oct 15;45(5):1105–1115. doi:10.1042/BST20160474. Epub 2017 Sep 12. PMID: 28900017.].
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 diet[63 - Morris M. C., Tangney C. C., Wang Y., Sacks F. M., Bennett D. A., Aggarwal N. T. MIND diet associated with reduced incidence of Alzheimer's disease. Alzheimer's Dement. 2015 Sep;11(9):1007-14. doi:10.1016/j.jalz.2014.11.009. Epub 2015 Feb 11. PMID: 25681666; PMCID: PMC4532650.].
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.
Конец ознакомительного фрагмента.
Текст предоставлен ООО «ЛитРес».
Прочитайте эту книгу целиком, купив полную легальную версию (https://www.litres.ru/pages/biblio_book/?art=69608131) на ЛитРес.
Безопасно оплатить книгу можно банковской картой Visa, MasterCard, Maestro, со счета мобильного телефона, с платежного терминала, в салоне МТС или Связной, через PayPal, WebMoney, Яндекс.Деньги, QIWI Кошелек, бонусными картами или другим удобным Вам способом.
notes
Сноски
1
Geroprotectors is the name given to a group of certain substances or therapeutic methods that help to increase longevity. Read more: Fomenko A. N., Proshkina E. N., Fedintsev A. Yu., Tsvetkov V. O., Shaposhnikov M. V., Moskalev A. A. "Potential geroprotectors." – Ed. note.
2
VSH25 is a project to prolong life and preserve health. Read more at vsh25.net. – Ed. note.
3
Accommodation of the eye is its ability to focus on objects at different distances by changing the refractive properties of the lens. – Ed. note.
4
López-Otín C., Blasco M. A., Partridge L., Serrano M., Kroemer G. The hallmarks of aging. Cell. 2013 Jun 6;153(6):1194-217. doi:10.1016/j.cell.2013.05.039. PMID: 23746838; PMCID: PMC3836174.
5
Jin K. Modern Biological Theories of Aging. Aging Dis. 2010 Oct 1;1(2):72–74. PMID: 21132086; PMCID: PMC2995895.
6
Van Heemst D. Insulin, IGF-1 and longevity. Aging Dis. 2010 Oct;1(2):147-57. Epub 2010 Aug 26. PMID: 22396862; PMCID: PMC3295030.
7
Immunosenescence begins at 5–7 years and completes by puberty, but small fragments of active glandular tissue persist throughout a human's life. – Ed. note.
8
Thomas R., Wang W., Su D. M. Contributions of Age-Related Thymic Involution to Immunosenescence and Inflammaging. Immun Ageing. 2020 Jan 20;17:2. doi:10.1186/s12979-020-0173-8. PMID: 31988649; PMCID: PMC6971920.
9
Freitas A. A., de Magalhães J. P. A review and appraisal of the DNA damage theory of aging. Mutat Res. 2011 Jul-Oct;728(1–2):12–22. doi:10.1016/j.mrrev.2011.05.001. Epub 2011 May 10. PMID: 21600302.
10
Yurov Y. B., Iourov I. Y., Monakhov V. V., Soloviev I. V., Vostrikov V. M., Vorsanova S. G. The variation of aneuploidy frequency in the developing and adult human brain revealed by an interphase FISH study. J Histochem Cytochem. 2005 Mar;53(3):385-90. doi:10.1369/jhc.4A6430.2005. PMID: 15750026.
11
Afanas'ev I. Signaling and Damaging Functions of Free Radicals in AgingFree Radical Theory, Hormesis, and TOR. Aging Dis. 2010 Oct;1(2):75–88. Epub 2010 Jul 12. PMID: 22396858; PMCID: PMC3295029.
12
Warner H. R., Hodes R. J., Pocinki K. What does cell death have to do with aging? J Am Geriatr Soc. 1997 Sep;45(9):1140-6. doi:10.1111/j.15325415.1997.tb05981.x. PMID: 9288026.
13
Ontogeny is the individual development of an organism. – Ed. note.
14
Razgonova M. P., Zakharenko A. M., Golokhvast K. S., et al. Telomerase and telomeres in aging theory and chronographic aging theory (Review). Mol Med Rep. 2020;22(3):1679–1694. doi:10.3892/ mmr.2020.11274.
15
Shay J. W., Wright W. E. Telomerase activity in human cancer. Curr Opin Oncol. 1996 Jan;8(1):66–71. doi:10.1097/00001622-199601000-00012. PMID: 8868103.
16
Furman D., Campisi J., Verdin E., et al. Chronic inflammation in the etiology of disease across the life span. Nat Med. 2019;25:1822–1832. doi:10.1038/s41591-019-0675-0.
17
Gomes M. J., Martinez P. F., Pagan L. U., et al. Skeletal muscle aging: influence of oxidative stress and physical exercise. Oncotarget. 2017 Mar 21;8(12):20428-20440.doi:10.18632/oncotarget.14670. PMID: 28099900; PMCID: PMC5386774.
18
Vargas-Mendoza N., Morales-González Á., Madrigal-Santillán E. O., et al. Antioxidant and Adaptative Response Mediated by Nrf2 during Physical Exercise. Antioxidants (Basel). 2019 Jun 25;8(6):196. doi:10.3390/antiox8060196. PMID: 31242588; PMCID: PMC6617290.
19
Brandao C. F. C., de Carvalho F. G., Souza A. O., et al. Physical training, UCP1 expression, mitochondrial density, and coupling in adipose tissue from women with obesity. Scand J Med Sci Sports. 2019 Nov;29(11):1699–1706. doi:10.1111/sms.13514. Epub 2019 Jul 22. PMID: 31282585.
20
Kanaley J. A. Growth hormone, arginine, and exercise. Curr Opin Clin Nutr Metab Care. 2008 Jan;11(1):50-4. doi:10.1097/MCO.0b013e-3282f2b0ad. PMID: 18090659.
21
Lou M., Zong X. F., Wang L. L. Curative treatment of hypertension by physical exercise. Eur Rev Med Pharmacol Sci. 2017 Jul;21(14):3320–3326. PMID: 28770948.
22
Hirshkowitz M., Whiton K., Albert S. M., et al. National Sleep Foundation's sleep time duration recommendations: methodology and results summary. Sleep Health. 2015 Mar;1(1):40–43. doi:10.1016/j. sleh.2014.12.010. Epub 2015 Jan 8. PMID: 29073412.
23
Kwak S., Kim H., Chey J., Youm Y. Feeling How Old I Am: Subjective Age Is Associated With Estimated Brain Age. Front Aging Neurosci. 2018;10:168. Published 2018 Jun 7. doi:10.3389/ fnagi.2018.00168.
24
Stephan Y., Sutin A. R., Terracciano A. Subjective Age and Mortality in Three Longitudinal Samples. Psychosom Med. 2018 Sep;80(7):659–664. doi:10.1097/PSY.0000000000000613. PMID: 29864106; PMCID: PMC6345273.
25
Povedano J. M., Martinez P., Serrano R., et al. Therapeutic effects of telomerase in mice with pulmonary fibrosis induced by damage to the lungs and short telomeres. Elife. 2018;7:e31299. Published 2018 Jan 30. doi:10.7554/eLife.31299.
26
Reich D., Green R., Kircher M., et al. Genetic history of an archaic hominin group from Denisova Cave in Siberia. Nature. 2010;468, 1053–1060. doi:0.1038/nature09710.
27
Venter J. C., Remington K., Heidelberg J. F., et al. Environmental genome shotgun sequencing of the Sargasso Sea. Science. 2004 Apr 2;304(5667):66–74. doi:10.1126/science.1093857.
28
Fraga M. F., Ballestar E., Paz M. F., et al. Epigenetic differences arise during the lifetime of monozygotic twins. Proceedings of the National Academy of Sciences of the United States of America. 2005;102(30), 10604-10609. doi:10.1073/pnas.0500398102.
29
Waterland R. A., Jirtle R. L. Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol Cell Biol. 2003;23(15):52935300. doi:10.1128/mcb.23.15.5293–5300.2003.
30
Ornish D., Magbanua M. J., Weidner G., et al. Changes in prostate gene expression in men undergoing an intensive nutrition and lifestyle intervention. Proceedings of the National Academy of Sciences of the United States of America. 2008;105(24), 8369–8374. doi:10.1073/ pnas.0803080105.
31
Rönn T., Volkov P., Davegårdh C., et al. A six months exercise intervention influences the genome-wide DNA methylation pattern in human adipose tissue. PLoS Genet. 2013 Jun;9(6):e1003572. doi:10.1371/journal.pgen.1003572. Epub 2013 Jun 27. PMID: 23825961; PMCID: PMC3694844.
32
Graff M., Scott R. A., Justice A. E., et al. Genome-wide physical activity interactions in adiposity – a meta-analysis of 200,452 adults. PLoS Genet. 2017;13(4):e1006528. doi:10.1371/journal.pgen. 1006528.
33
Massachusetts General Hospital. (2019, November 5). Physical activity may protect against new episodes of depression. Science Daily. www.sciencedaily.com/releases/2019/11/191105113510.htm (http://www.sciencedaily.com/releases/2019/11/191105113510.htm).
34
Joehanes R., Just A. C., Marioni R. E., et al. Epigenetic Signatures of Cigarette Smoking. Circ Cardiovasc Genet. 2016;9(5):436–447. doi:10.1161/CIRCGENETICS.116.001506.
35
Garaycoechea J., Crossan G., Langevin F., et al. Alcohol and endogenous aldehydes damage chromosomes and mutate stem cells. Nature. 2018;553, 171–177. doi:10.1038/nature25154.
36
Schrott R., Acharya K., Itchon-Ramos N., et al. Cannabis use is associated with potentially heritable widespread changes in autism candidate gene DLGAP2 DNA methylation in sperm. Epigenetics. 2020;15(1–2):161–173. doi:10.1080/15592294.2019.1656158.
37
Slotkin T. A., Skavicus S., Levin E. D., Seidler F. J. Paternal. 9-Tetrahydrocannabinol Exposure Prior to Mating Elicits Deficits in Cholinergic Synaptic Function in the Offspring. Toxicological Sciences. 2020 Apr;174(2), 210–217. doi:10.1093/toxsci/kfaa004.
38
Madaniyazi L., Li S., Li S., Guo Y. Candidate gene expression in response to low-level air pollution. Environ Int. 2020 Jul;140: 105610. doi:10.1016/j.envint.2020.105610. Epub 2020 Apr 2. PMID:32248990.
39
Noniashvili E. M., Grudinina N. A., Kustova V. E., etc. DNA methylation in early mouse embryogenesis influenced by bisphenol A. Ecological genetics. 2017. 15 (3). P. 42–53.
40
Anway M. D., Cupp A. S., Uzumcu M., Skinner M. K. Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science. 2005 Jun 3;308(5727):1466-9. doi:10.1126/science.1108190. Erratum in: Science. 2010 May 7;328(5979):690. PMID: 15933200.
41
Kiecolt-Glaser J. K., Loving T. J., Stowell J. R., et al. Hostile marital interactions, proinflammatory cytokine production, and wound healing. Arch Gen Psychiatry. 2005;62(12):1377–1384. doi:10.1001/ archpsyc.62.12.1377.
42
Sender R., Fuchs S., Milo R. Revised Estimates for the Number of Human and Bacteria Cells in the Body. Published: August 19, 2016. doi:10.1371/journal.pbio.1002533.
43
Spalding K. L., Bhardwaj R. D., Buchholz B. A., Druid H., Frisén J. Retrospective Birth Dating of Cells in Humans. doi:10.1016/j. cell.2005.04.028PlumX Metrics.
44
Kong S., Zhang Y. H., Zhang W. Regulation of Intestinal Epithelial Cells Properties and Functions by Amino Acids. doi:10.1155/2018/ 2819154.
45
Azevedo F. A. C., Carvalho L. R. B., Grinberg L. T., et al. Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled-up primate brain. Published: 18 February 2009 doi:10.1002/cne.21974.
46
Chemical element is a type of atom that has certain chemical properties. The adult body consists of more than 60 chemical elements – Ed. note.
47
Alberts B., Johnson A., Lewis J., et al. Molecular Biology of the Cell. 4th edition. The Chemical Components of a Cell. https://www.ncbi.nlm.nih.gov/books/NBK26883/#A166 (https://www.ncbi.nlm.nih.gov/books/NBK26883/#A166).
48
Zaidi Z. F. Gender Differences in Human Brain: A Review. The Open Anatomy Journal. 2010;2:37–55. https://benthamopen.com/AB-STRACT/TOANATJ2-37.
49
Von Bartheld C. S., Bahney J., Herculano-Houzel S. The search for true numbers of neurons and glial cells in the human brain: A review of 150 years of cell counting. J Comp Neurol. 2016;524(18):3865–3895. doi:10.1002/cne.24040.
50
Synapses are divided into chemical, electrical, and mixed. – Ed. note.
51
Von Bartheld C. S., Bahney J., Herculano-Houzel S. The search for true numbers of neurons and glial cells in the human brain: A review of 150 years of cell counting. J Comp Neurol. 2016 Dec 15;524(18):3865–3895. doi:10.1002/cne.24040. Epub 2016 Jun 16. PMID: 27187682; PMCID: PMC5063692.
52
The gut-brain axis includes the entire pool of intestinal microorganisms (microbiota), the "intestinal brain" and the central nervous system. – Ed. note.
53
Banks W. A., Reed M. J., Logsdon A. F., et al. Healthy aging and the blood-brain barrier. Nat Aging. 2021;1:243–254. doi:10.1038/s43587-02100043-5.
54
Tobin M. K., Musaraca K., Disouky A., Shetti A., Bheri A., Honer W. G., Kim N., Dawe R. J., Bennett D. A., Arfanakis K., Lazarov O. Human Hippocampal Neurogenesis Persists in Aged Adults and Alzheimer's Disease Patients. Cell Stem Cell. 2019 Jun 6;24(6):974–982.e3. doi:10.1016/j.stem.2019.05.003. Epub 2019 May 23. PMID: 31130513; PMCID: PMC6608595.
55
Nokia M. S., Lensu S., Ahtiainen J. P., Johansson P. P., Koch L. G., Britton S. L., Kainulainen H. Physical exercise increases adult hippocampal neurogenesis in male rats provided it is aerobic and sustained. J Physiol. 2016;594: 1855–1873. doi:10.1113/JP271552.
56
Phillips C. Lifestyle Modulators of Neuroplasticity: How Physical Activity, Mental Engagement, and Diet Promote Cognitive Health during Aging. Neural Plast. 2017;2017:3589271. doi:10.1155/2017/3589271. Epub 2017 Jun 12. PMID: 28695017; PMCID: PMC5485368.
57
Dinoff A., Herrmann N., Swardfager W., et al. The Effect of Exercise Training on Resting Concentrations of Peripheral Brain-Derived Neurotrophic Factor (BDNF): A Meta-Analysis. PLOS One. 2016;11(9): e0163037. doi:10.1371/journal.pone.0163037.
58
Li P., Legault J., Litcofsky K. A. Neuroplasticity as a function of second language learning: anatomical changes in the human brain. Cortex. 2014 Sep;58:301-24. doi:10.1016/j.cortex.2014.05.001. Epub 2014 May 17. PMID: 24996640.
59
Fox K. C., Nijeboer S., Dixon M. L., et al. Is meditation associated with altered brain structure? A systematic review and meta-analysis of morphometric neuroimaging in meditation practitioners. Neurosci Biobehav Rev. 2014 Jun;43:48–73. doi:10.1016/j.neubiorev.2014.03.016. Epub 2014 Apr 3. PMID: 24705269.
60
Devore E. E., Kang J. H., Breteler M. M., Grodstein F. Dietary intakes of berries and flavonoids in relation to cognitive decline. Ann Neurol. 2012 Jul;72(1):135-43. doi:10.1002/ana.23594. Epub 2012 Apr 26. PMID: 22535616; PMCID: PMC3582325.
61
Farzaei M. H., Rahimi R., Nikfar S., Abdollahi M. Effect of resveratrol on cognitive and memory performance and mood: A meta-analysis of 225 patients. Pharmacol Res. 2018 Feb;128:338–344. doi:10.1016/j. phrs.2017.08.009. Epub 2017 Aug 26. PMID: 28844841.
62
Calder P. C. Omega-3 fatty acids and inflammatory processes: from molecules to man. Biochem Soc Trans. 2017 Oct 15;45(5):1105–1115. doi:10.1042/BST20160474. Epub 2017 Sep 12. PMID: 28900017.
63
Morris M. C., Tangney C. C., Wang Y., Sacks F. M., Bennett D. A., Aggarwal N. T. MIND diet associated with reduced incidence of Alzheimer's disease. Alzheimer's Dement. 2015 Sep;11(9):1007-14. doi:10.1016/j.jalz.2014.11.009. Epub 2015 Feb 11. PMID: 25681666; PMCID: PMC4532650.