1. Zhuravleva T.P. Fundamentals of Geriatrics: Textbook. manual for students of institutions of environments. prof. education. M .: FORUM: INFRA. M., 2003.271 p.

2. Lobachev A.N. Mitochondrial biogenesis during cell differentiation and aging. VINITI 19.09.85, No. 6756-B85 Dep., 1985, p. 28.

3.https: //ru.m.wikipedia.org/wiki/Human_Aging

4. Guidelines for Gerontology and Geriatrics: Clinical Geriatrics / Edited by V.N. Yarygina, A.S. Melentyev. M .: GEOTAR-MED, 2003.523 p.

Today there are several alternative theories that partly contradict each other and partly complement each other. Modern biology pays great attention to the problem of aging, and every year new facts appear that allow a deeper understanding of the mechanisms of this process.

Molecular genetic theories. The hypothesis that the cause of aging is changes in the genetic apparatus of the cell is one of the most recognized in modern gerontology. Molecular genetic theories are divided into two large groups. Some scientists consider age-related changes in the genome as hereditarily programmed. Others believe that aging is the result of the accumulation of random mutations. Hence it follows that the aging process can be either a natural result of the growth and development of an organism, or a consequence of the accumulation of random errors in the system of storage and transmission of genetic information.

Free radical theory. Almost simultaneously put forward by D. Harman (1956) and N.M. Emanuel (1958), the free radical theory explains not only the mechanism of aging, but also a wide range of associated pathological processes (cardiovascular diseases, weakened immunity, brain dysfunctions, cataracts, cancer, and some others). According to this theory, the cause of cell dysfunction is the free radicals necessary for many biochemical processes - reactive oxygen species synthesized mainly in mitochondria - the energy factories of cells. If a very aggressive, reactive free radical accidentally leaves the place where it is needed, it can damage DNA, RNA, proteins and lipids. Nature has provided a mechanism for protection against excess free radicals: in addition to superoxide dismutase and some other enzymes synthesized in mitochondria and cells, many substances that enter the body with food have an antioxidant effect - including vitamins A, C and E. Regular consumption of vegetables and fruits, and even a few cups of tea or coffee a day will provide you with an adequate dose of polyphenols, which are also good antioxidants. Unfortunately, an excess of antioxidants - for example, with an overdose of dietary supplements - is not only unhealthy, but can even intensify oxidative processes in cells.

Aging is a mistake. The hypothesis of "aging by mistake" was put forward in 1954 by the American physicist M. Szilard. Investigating the effects of radiation on living organisms, he showed that the effect of ionizing radiation significantly reduces the lifespan of people and animals. Radiation causes numerous mutations in the DNA molecule and initiates some of the symptoms of aging, such as gray hair or cancers. From his observations, Szilard concluded that mutations are the direct cause of aging in living organisms. However, he did not explain the fact of aging of people and animals that were not exposed to radiation. His follower L. Orgel believed that mutations in the genetic apparatus of a cell can either be spontaneous, or arise in response to aggressive factors - ionizing radiation, ultraviolet radiation, exposure to viruses and toxic (mutagenic) substances, etc. Over time, the DNA repair system wears out, resulting in aging of the body.

Apoptosis theory. Academician V.P. Skulachev calls his theory the theory of cellular apoptosis. Apoptosis is a process of programmed cell death. As trees get rid of parts in order to preserve the whole, so each individual cell, having passed its life cycle, must die out and a new one must take its place. If a cell becomes infected with a virus, or a mutation occurs in it, leading to malignancy, or simply expires, then, in order not to endanger the entire organism, it must die. Unlike necrosis - the violent death of cells due to trauma, burns, poisoning, lack of oxygen as a result of clogging of blood vessels, etc., with apoptosis, the cell neatly disassembles itself, and neighboring cells use its fragments as a building material. Mitochondria also undergo self-liquidation - having studied this process, Skulachev called it mitoptosis. Mitoptosis occurs when too many free radicals are produced in the mitochondria. When the number of dead mitochondria is too large, their decay products poison the cell and lead to its apoptosis. Aging, from the point of view of Skulachev, is the result of the fact that more cells die in the body than are born, and the dying functional cells are replaced by connective tissue. The essence of his work is the search for methods to counteract the destruction of cellular structures by free radicals. According to the scientist, old age is a disease that can and should be treated, the aging program of the body can be disabled and thereby turn off the mechanism that shortens our life. According to Skulachev, the main reactive oxygen species leading to the death of mitochondria and cells is hydrogen peroxide. He is currently testing SKQ, a drug designed to prevent signs of aging.

The theory of somatic mutations. Many studies have shown an increase with age in the number of somatic mutations and other forms of DNA damage, suggesting DNA repair (repair) as an important factor in supporting cell longevity. DNA damage is typical of cells, and is caused by factors such as hard radiation and reactive oxygen species, and therefore DNA integrity can only be maintained through repair mechanisms. Indeed, there is a relationship between longevity and DNA repair, as demonstrated by the enzyme poly-ADP-ribose-polymerase-1 (PARP-1), an important player in the cellular response to stress-induced DNA damage. Higher PARP-1 levels are associated with longer life expectancy.

The theory of bacterial intoxication of the body. An original hypothesis was put forward by the outstanding Russian biologist I.I. Mechnikov (1845-1916), who considered aging to be the result of intoxication of the body with metabolic products of bacteria living in the intestinal tract and products of nitrogen metabolism of the body itself (uric acid). Poisonous substances are formed, including skatole, indole, phenol (carbolic acid), cresol, cadaverine (cadaveric poison), tyramine and other toxins.

Olovnikov's telomeric theory. In many human cells, the loss of their ability to divide is associated with the loss of telomeres at the ends of chromosomes, after a certain number of divisions. This is due to the absence of the enzyme telomerase, which is usually expressed only in germ and stem cells. It has recently been found that oxidative stress can also have an effect on telomere loss, significantly accelerating this process in certain tissues.

Currently, there is no main theory of aging, they all occupy an important place in science.

Bibliographic reference

Melikhova L.V., Chentieva L.A., Lushchik M.V. BASIC THEORY OF AGING // International student scientific bulletin. - 2016. - No. 4-2 .;
URL: http://eduherald.ru/ru/article/view?id=16084 (date accessed: 12/25/2019). We bring to your attention the journals published by the "Academy of Natural Sciences"

Aging is a natural process. And therefore it is impossible to prevent old age and death, but prolonging life is a responsible and noble task of modern medicine.

Knowledge of the laws governing the development of aging, its mechanisms is necessary for the doctor to objectively assess health, predict the possible life expectancy and the reasons for the development of diseases. Diseases such as atherosclerosis, arterial hypertension, ischemic heart and brain disease, diabetes, cancer occur mainly in the second half of a person's life and are often associated with the aging process. That is why the most effective means of preventing these diseases are effects aimed at the rate of aging.

The origins of gerontology go back to ancient times. In the treatises and teachings of ancient medicine, a person's desire to prolong life and actively influence human longevity can be traced. Recommendations for achieving longevity are available in the collections of Hippocrates, Avicenna's canon of medical science, and the ancient Indian Vedas. In Russia, physician Fischer was the first to highlight these issues in print in his book "On old age, its degrees and diseases" In the 18th century.

It is necessary to strictly distinguish between the concepts of aging and old age, cause and effect. Old age - the naturally coming final period of age development. Aging - a destructive process that develops as a result of the damaging effect of exogenous and endogenous factors that grows with age, leading to a failure of the physiological functions of the body. Aging leads to a limitation of the body's adaptive capabilities, a decrease in its reliability, and the development of age-related pathology. Environmental factors, affecting biological processes, affect life expectancy. In the course of evolution, along with aging, the process of vitaukt arose . Vitaukt - a process that stabilizes the body's vital functions, increases its reliability, aimed at preventing damage to living systems with age and increasing life expectancy. Aging and vitaukta processes occur along with the inception of the organism. The change in their relationship also divides all individual development into three periods - progressive, stable, degrading.

There are individual characteristics of aging that are peculiar to individuals.

Natural (physiological) aging characterized by a certain rate and sequence of age-related changes corresponding to the biological, adaptive and regulatory capabilities of a given human population. It is determined by sex, species, genotype. According to statistics, about 40% of centenarians have a favorable heredity.

Premature (accelerated) aging characterized by the earlier development of age-related changes or their greater severity in a particular age period. Premature aging is promoted by past diseases, unfavorable environmental factors, including stressful situations that can affect different links in the chain of age-related changes, accelerate, distort, and intensify their usual course.

Slow motion (retarded)aging leading to an increase in life expectancy, longevity. Age-related changes in these cases occur much later.

Aging is associated with changes occurring at all levels of organization of living matter - molecular, subcellular, cellular, systemic, whole organism.

The development of aging is characterized by:

- heterochronism - the difference in the onset of aging of individual organs and tissues. Atrophy of the thymus, for example, in humans begins at the age of 13-15 years, the gonads - in the climacteric period (48-52 years in women), and some functions of the pituitary gland remain at a high level until old age.

- heterotopicity - the severity of aging processes is not the same for different organs and different structures of the same organ (for example, aging of the fascicular zone of the adrenal cortex is less pronounced than glomerular).

- heterocaphteness b - age-related changes in the body develop in different directions. For example, the secretion of sex steroid hormones decreases, and the gonadotropic hormones of the pituitary gland increase.

- heterokineticity – age-related changes in the body develop at different rates. For example, changes in the musculoskeletal system increase slowly with age; shifts in a number of brain structures occur late, but rapidly progress, disrupting its function.

One of the main regularities of the aging of an organism is a decrease in its adaptive and regulatory capabilities, i.e. reliability. These changes are of a staged nature. With aging, the ability to adapt to significant loads first decreases and, ultimately, the level of metabolism and function changes, even at rest.

From the Middle Ages to the present day, the search for means to rejuvenate and prolong life continues, and people continue to age and die. A significant contribution to the formation of modern ideas about the essence of aging was made by the classics of Russian biology - I.I. Mechnikov, I. II. Pavlov, A.V. Nagorny, A.A. Bogomolets. Their research is characterized by the search for the fundamental mechanisms of aging and the desire to develop tools that affect life expectancy.

I.I. Mechnikov put forward an autointoxication theory, which states that aging is the result of the body's autointoxication associated with intestinal function. In search of an antidote, he visited Bulgaria, in a village famous for a large number of centenarians. He learned that the patriarchs of this area feed mainly on sour milk. Having studied the microbe that oxidizes milk, he created the famous Bulgarian bacillus, which became a patented medicine. Mechnikov's discovery was widely recognized in Russia, but still it did not turn out to be the "elixir of youth."

I.P. Pavlov linked the leading mechanisms of aging with changes in nervous activity. Scientists of his school discovered the most important patterns of age-related changes in higher nervous activity.

A.A. Bogomolets believed that the leading mechanisms of aging are determined by age-related changes in connective tissue. On the basis of these ideas, he proposed using cytotoxic sera for a positive effect on the body in old age.

A.V. Nagorny and his school collected a large amount of factual material about the characteristics of the course of aging and connected this process with the damping self-renewal of protoplasm.

Currently, there are two traditional points of view on the causes of aging.

1. Aging is a genetically programmed process, the result of the natural development of a program embedded in the genetic apparatus. In this case, the action of environmental and internal factors can affect, but to a small extent, the rate of aging.

2. Aging is the result of the destruction of the organism as a result of the inevitable damaging effect of the shifts that occur in the course of life itself - a stochastic, probabilistic process. In other words, aging is a destructive, probabilistic process that develops in an organism with genetically programmed properties.

Aging is a multi-causal process caused by many factors, the action of which is repeated and accumulated throughout life. Among them are stress, illness, activation of free radical oxidation and accumulation of peroxide metabolic products, exposure to xenobiotics (foreign substances), insufficient excretion of protein breakdown products, hypoxia, etc.

Aging is a multifocal process... It occurs in different structures of the cell - the nucleus, mitochondria, membranes, etc .; in different types of cells - nerve, secretory, immune, hepatic, etc. The rate of age-related changes is determined by the ratio of aging and vitauct. Vitaukt means not just the restoration of damage that occurs during the aging process, it is a mechanism for maintaining the reliability of the body, the ability to recover, to compensate for the violations that have arisen.

Age classifications.

One of the main issues in gerontology is the question of age. There is an international classification of age groups:

Under 45 years old - young age

45 - 59 years old - average age

60 - 74 years old

75 - 90 years old age

More than 91 years - long-livers.

All these age periods are conditional, the boundaries are individual and represent an individual development.

Several definitions of age have been proposed:

1. Age- the duration of the existence of an organism from the moment of birth to the present time in any time scale.

2. Calendar(passport, chronological) - expressed in a calendar scale, that is, measured by the number of rotations around the sun.

3. Biological - the degree of true health, the level of vitality and general health of the body, all its functions.

There are several types of old age: chronological, physiological, psychological and social. All types of old age are interconnected and have one or another effect on each other.

Chronological (calendar) old age- the number of years lived. The opinions of scientists in the definition of calendar old age were divided. The German scientist pathologist L. Aschoff considered the onset of old age from 65 to 85 years. Modern English physiologists claim that old age occurs after 50 years. Soviet demographers S.T. Strumilin and B.Ts. Urlanis old age was subdivided into old age (60-69), early old age (70-79), deep old age - after 80 years.

Physiological (physical) old age it is more difficult to classify and set age barriers, because the process of physical aging is largely individual. At the same old age, some people may be healthy and not old, while others, in terms of their health, seem to be ahead of their age. In the same person, different organs wear out to varying degrees and not simultaneously.

Psychological old age. This type of old age can be defined as the moment in a person's life when he himself begins to recognize himself as old. A person may realize this too early, or too late.

Social old age. This old age depends on the age of the whole society as a whole. Social age is correlated with the average life expectancy in a particular country in a certain period of time. In Zambia, Mali, Afghanistan, where the average life expectancy is 43 - 44 years, old people are "younger" than in Japan, Canada, Switzerland.

Aging is more social than a biological process, different for different eras and cultures, for representatives of different social strata and groups. The higher the level of aging of the population as a whole, the further the individual border of old age is pushed back. The onset of social old age depends not only on the demographic aging of the population, but also on the conditions of work and rest, sanitary and hygienic conditions, the level of health care and social security, culture and education, environmental safety and the development of social production, satisfaction of material and spiritual needs. The presence of bad habits, chronic diseases, trauma, heredity is also important.

Life expectancy is determined, as it were, by a "college" of socio-economic and political factors.

TEACHING AND METHODOLOGICAL GUIDE

Chelyabinsk

Ural Academy

Federal State Budgetary Educational Institution

higher professional education

"Ural State University

physical culture "

Department of Sports Medicine and Physical Rehabilitation

A. V. Skutin

PHYSICAL REHABILITATION IN GERONTOLOGY: SELECTED LECTURES

Study guide

for undergraduates of the direction of training 034400.68 "Physical culture for persons with disabilities in health (Adaptive physical culture)" program "Physical rehabilitation"

Chelyabinsk

Methodical Council of UralSUPC

protocol no. 3 from 19.11. 2014

Reviewers:

Professor, head. Department of Medical Rehabilitation and Sports Medicine, State Budgetary Educational Institution SUSMU of the Ministry of Health of the Russian Federation, MD A.S. Sabiryanov

Professor of the Department of Sports Medicine and Physical Rehabilitation of Ural State University of Physical Culture., MD Sabiryanova E.S.

Skutin, A. V.

Physical rehabilitation in gerontology (selected lectures): textbook. - method. manual for undergraduates in the direction of training 034400.68 "Physical culture for persons with disabilities in health (Adaptive physical culture)" / A. V. Skutin. - Chelyabinsk: Ural Academy, 2014 .-- 147 p.

The work describes in detail the terms most used in the literature on physical rehabilitation in gerontology. In addition, the manual provides data on the founders of gerontology and geriatrics, and sets out in detail various theories of aging. The main physiological and pathophysiological processes of aging in elderly and senile people are described.

The work is structured: it consistently provides data on the sections of gerontology, describes the clinical and physiological picture of human aging and the processes of slowing aging (vitaukt), provides the main postulates of disease prevention in old and senile age, describes a variety of modern geroprotectors.

The teaching aid is intended for undergraduates in the direction of training 034400.68 "Physical culture for persons with disabilities (Adaptive physical culture)".

Lecture number 1. Introduction Gerontology is the science of old age and aging. Development prospects, sections of gerontology. A brief historical overview ……………………………………………………………………… ......... 6

Lecture number 2. Aging and old age …………………………………… ...... 12

Lecture number 3. Aging and the sequence of ontogenetic processes. Constitutional features, belonging to a certain ecological-population group, the influence of social factors. Biological age of men and women …………………………………… 14

Lecture number 4. General laws and theories of aging ………… ......... 21

Lecture number 5... Molecular and cellular mechanisms of aging ... ......... 34

Lecture number 6. Medical and social importance of elderly and senile people. Fundamentals of General Geriatrics. Aging and disease .......... 36

Lecture No. 7. Methods for researching the level of health of elderly and senile people. Aging of the main functional systems of the body. Clinical manifestation of involutional processes ... ... ......... 41

Lecture number 8. Care and rehabilitation. General care for the elderly and senile people ............................................. 62

Lecture number 9... Physiotherapy. Sanatorium treatment ……… ....... 78

Lecture number 10. Features of the use of medicines in the practice of geriatrics …………… .. ……………………………………… ........ 84

Lecture number 11... Advances in molecular biology and priorities of gerontology at the beginning of the XXI century …………………………………… .......... 93

Lecture number 12. Means for the prevention of premature aging (geroprotectors) ……………………………………………………………………………………………………………………………… .. 95

Lecture number 13. Aging as a psychological phenomenon. Progeria, the phenomena of programmed self-destruction, senile mental disorders ..................... 100

Lecture number 14. Aging prevention …………………………… ....... 111

Lecture number 15. Modern research methods in gerontology ..... 115

Lecture number 16. The phenomenon of human longevity ... ... ... .................... 119

Lecture number 17... Physiotherapy exercises in the practice of geriatrics ... ... ......... 137

LIST OF USED SOURCES............................146

Lecture number 1.

Introduction. Gerontology is the science of old age and aging.
Development prospects, sections of gerontology. A brief historical outline

"The disease is premature

acquired old age.

Old age is a natural disease "

Aristotle

“Old age is a bad habit,

for which active people have no time "

André Maurois

“Getting old is boring,

but this is the only possibility
live long "

“Our century is short-lived. No wonder us
to seduce with reworked old stuff. We believe that we were born. All that we learn from our ancestors "

P. Shakespeare. 123rd sonnet

Change in the age structure of the population towards its aging -
a distinctive feature of the modern era. Since 1950, the relative share of people over 65 in the population of economically developed countries has doubled and
is 13-14%, and by 2020 it will increase to 20%. Demographically
the old population in the 21st century will become typical for all countries.

In line with the action plan formulated by the World
the UN Assembly on Aging Programs, held in Vienna in 1982, during
many countries of the world have developed and are developing programs for
improving the health and quality of life of elderly people and
old age. The problem of rehabilitation of the elderly is related to
social sections of national programs.

Speaking about the prerequisites for rehabilitation, there is a high degree of
loneliness, longing and isolation in the elderly. At the same time, they are capable of
not only work, but also learn and adapt to new conditions. This
a tragic situation gives the elderly a sense of worthlessness,
aggravated in the conditions of a modern industrial society, in
where there is a cult of youth and a disdain for
old age.

Human health and the very duration of his life are closely related to the nature of the aging of the body. The science of aging - gerontology (from the Greek geron, genus gerontos - old man, old man) studies the normal aging process of a person, its main manifestations and factors influencing the nature, rate and intensity of senile changes. Geriatrics is closely related to gerontology - a field of medicine that studies the diseases of elderly and senile people. Gerontology should occupy an important place in the curriculum for valeology as a health science, especially since many changes, which are later called senile, can begin quite early - in adulthood or even in youth. The basis of gerontology is the biology of aging, however, the problem of aging is inherently complex: biomedical, psychological.

The origins of clinical geriatrics in Russia are associated with the ideas of S.P. Botkin and the works of his students, published in the 90s. XIX century. Thoughts SP. Botkin on the theory of human aging, the characteristics of age-related changes in the development and course of atherosclerosis and some others
diseases in the elderly were reflected in the works of his students and staff. The term “geriatrics” was proposed in 1914 by the American physician J. L. Ncher, who not only proposed it, but also substantiated the requirement to single out geriatrics as an independent specialty.

In our country since the 50s. of the last century, the main research was carried out at the Institute of Gerontology of the USSR Academy of Sciences in Kiev, as well as in numerous research institutes and at the departments of medical institutes.

Geriatrics- the science of diseases of elderly and senile people.

By analogy with pediatrics, if pediatrics studies the diseases of the child's body, then geriatrics studies the diseases of the elderly.

The main tasks of geriatrics are to clarify, on the basis of data on the biology of human aging, the characteristics of the clinical course, diagnosis, treatment and prevention of premature aging. A. Stormer (1983) indicates that on average 3-4 diseases are established in men, and 5.2 in women. However, the reality is much more complicated. In many cases, the pathology of an elderly and old person can be compared to an iceberg, more than 6/7 of which is hidden under water. To reveal this hidden part of the iceberg, you need a detailed study of the patient's body, a good knowledge of not only the age-related characteristics of the course of internal diseases, but also the symptoms of the main diseases of the nervous, genitourinary systems and the musculoskeletal system.

When examining elderly people, diagnostic errors are more often observed. This is due to the fact that in old age there is a different reaction of the body to the disease, the presence of frequent complications, as well as the interpretation of the symptoms of the disease that has appeared by the patient himself as a manifestation of old age, and therefore he does not seek medical help in a timely manner. The whole concept of "aging" is essentially applied science. It covers a group of influences that we have identified because of their destructive effect, in other words, because people do not like them.

Some theoretical biologists have gone bankrupt in this area, developing philosophical skepticism about whether aging represents any "definite entity" at all. In an abstract sense, it really is no more so than a disease. However, these same biologists, as they approach the age of seventy, will undoubtedly face a number of changes that, over some foreseeable period of time, should lead to death. Since biology is not just a form of idle curiosity, its purpose is to create ways to keep people active and healthy for a longer time than they have hitherto, in other words, to prolong the life of an individual person. Nowadays, people rightly expect that "science" will ensure the fulfillment, or at least find ways to realize the long-standing aspirations of man, which our ancestors tried unsuccessfully to implement with the help of magic, or at least find the means for this.

Under the influence of the research necessary for the realization of these aspirations, the nature of the aspirations themselves changes, which become realistic; so, in our time, most people prefer longevity, which is attainable, unrealizable physical immortality. Incidentally, the term "potential immortality" is disappearing from the biological literature.

It is possible that gerontologists will have to defend more than once the legitimacy of the formulation of the problem of extending human life, especially in our time, when there are scientists seeking to find ethical arguments against the advisability of extending human life, at least in those societies to which they themselves do not belong.

We have seen that aging, biologically speaking, is not a well-defined concept. In most animals, it is observed only under artificial conditions, and for most of us, it would probably be pointless to spend so much effort on such an arbitrarily isolated part of ontogenesis, if the main aspiration of people was not connected with this. And since this is so, medicine has always considered the extension of an active life one of its most obvious goals. Gerontology differs from other branches of medical biology in that, while most medical research is aimed at making the human survival curve rectangular, gerontology seeks to lengthen this rectangle and push the inflection point as far as possible. Quotes by authors such as Vogt deserve the reproach thrown by James Parkinson (1755-1824): "If the population is not satisfied with the means of subsistence, it is not nature that is to blame, but the inability of politicians to discover hidden flaws in the laws on the distribution and appropriation of property." The postponement of the onset of old age, like other achievements in the field of environmental management, must be accompanied by appropriate restructuring of society.

Social, economic and political factors undoubtedly play a leading role in preventing death in pre-old age. However, no matter what problems arise in connection with the future increase in the species age of a person, medicine can afford to relate to
all protests based on selfish and wrong
interpreting the biology of human communities with the contempt they deserve as a mixture of ignorance and pseudoscience.

The fascination of researchers of previous years with magical rejuvenation did not benefit the development of science, but it was, at least, a completely humane occupation.

The possible social consequences of longevity, which are probably the most important practical aspect, have not been considered at all in this book. The entire course of evolution testifies to the existence of a connection between survival in old age and the presence of social life forms.

Over the past 160 years, life expectancy in economically developed countries has steadily increased at an average rate of three months per year. This phenomenon, as well as a significant aging of the population of economically developed and developing countries, that is, an increase in the proportion of the elderly in its structure, which became especially noticeable in the last quarter of the 20th century (Schulz-Aellen, 1997; Vaupel et al., 1998; Tinker, 2002; Kalache, Gatti, 2003), caused a natural and significant increase in interest in gerontology and, above all, in the study of the primary mechanisms of aging of organisms and populations and factors that determine life expectancy.

Gerontology (Greek geron, geront (os) - old man + logos doctrine) is a science that studies the laws of aging of living beings, including humans, and old age. For the first time the term was proposed by I.I.Mechnikov in 1903 (quoted from: Mechnikov, 1988). In Etudes of Optimism, Ilya Ilyich emphasized that the study of old age is not only of great theoretical interest, but at the same time of practical importance. Modern gerontology is an interdisciplinary science that includes the biology of aging, clinical gerontology (geriatrics), gerontopsychology, and social gerontology (hygiene). The term "geriatrics" was introduced in 1909 by the American physician I. L. Nasher. In 1914, he published the first book in the United States, entitled Geriatrics: Diseases of Old Age and Their Treatment.

The task of the biology of aging is to elucidate the primary mechanisms of aging in organisms and populations and the factors that determine life expectancy. The study of the biology of aging includes both experimental studies on animals of various species and clinical studies of humans at different periods of life. Population aging is one of the most important problems, which is currently acquiring great importance for the economic and social policies of not only developed but also developing countries. All over the world, more and more people are living to old (60–74 years) and old age. At the present time and in the future for several generations, most people have a sufficient opportunity to live to 75 years or more. In the coming years, further gradual aging of the population is expected, with a predominant increase in the elderly (75 years and older).

Attention to the problems of geriatrics in health care and social care institutions, all medical workers and persons working in related fields related to the provision of geriatric care, is becoming increasingly important in solving both individual problems of pensioners, aimed at preserving their physical, mental and
social health, and tasks related to the economy of the state, the growth of the well-being of the entire population of the country.

There are many problems that are common to
older age groups and the entire population. At the same time, some of them reflect the specific characteristics and needs characteristic of the elderly and senile people.

First of all, these are the issues of providing medical and social assistance. The problems of continuing to work, preparing for the transition to retirement age, and determining a rational lifestyle are inseparable from them.

Progressive aging of the population of developed countries and
the problems associated with it against the background of advances in biology and medicine have stimulated the development of gerontology.

Gerontology (the science of aging) has three main sections.

The biology of aging- a section of gerontology that combines
the study of the aging process of living organisms (higher animals and humans) at different levels of their organization: subcellular, cellular, tissue, organ and systemic. The study of the aging of a whole organism unites the activities of biologists and physicians - from specialists in the field of molecular biology and genetics to specialists in the field of experimental and clinical physiology, pathophysiology, pathomorphology, etc. The results of their work contribute to understanding
mechanisms of normal aging of animals and humans, reveal the reasons for the development of pathological processes inherent in the aging body, the characteristics of the course of various diseases in people of older age groups.

Geriatrics, or geriatric medicine - teaching about diseases of elderly and senile people: the peculiarities of their clinical course, treatment, prevention, organization of medical and social assistance.

Geriatric medicine studies diseases that mainly accompany old age: memory loss, senile dementia, osteoporosis, hip fracture, adenoma and prostate cancer. Diseases characteristic of other age groups, but with specific features in old age (atherosclerosis with its complications, symptomatic arterial hypertension, hypertension, heart failure, late-onset diabetes mellitus, chronic nonspecific lung diseases, mental depression, oncological diseases, etc.).

Social gerontology studies the influence of living conditions on the aging process of a person and develops measures aimed at eliminating the negative impact of environmental factors. It is a teaching about the relationship between the age of an aging person, his health and performance in the environment.

Social gerontology deals with the issues of sanitary statistics, the influence of the factor of population aging on the development of the country and, conversely, the development of the country on the level of provision of the elderly, the position of elderly people in the family and society, intergenerational relationships, etc.

Social gerontology unites ideas about the way of life of an aging person (work at pre-retirement and retirement age, food hygiene, rest, physical activity, personal hygiene, etc.), and also finds out the reasons for early occupational aging.

1 Give the definition of gerontology and geriatrics.

2 Name the main sections of gerontology, give their definitions.

Lecture number 2

Aging and old age

For a long time, life and death in an idealistic and vulgar
materialistic philosophy was seen as two categories that deny each other. The true definition of their relationships was given by F. Engels: “Even now physiology is not considered scientific that does not consider death as an essential moment of life, that does not understand that the denial of life is essentially contained in life itself, so that life is always thought of in terms of with its necessary result, which is constantly in its embryo - death. The dialectical understanding of life is precisely what comes down to ”.

Thus, in the course of life, aging is formed, which ultimately denies life, leading to the death of the organism. Diseases such as atherosclerosis, arterial hypertension, ischemic heart and brain disease, diabetes, cancer occur mainly in the second half of a person's life and are often associated with the aging process. This is why the most
Effective means of preventing these diseases are effects aimed at the rate of aging. With different combinations and varying degrees of clinical symptoms, the following are observed: atherosclerotic lesions of the vessels of the heart and brain (ischemic heart disease, atherosclerotic encephalopathy), arterial symptomatic hypertension, hypertension, pulmonary emphysema, neoplastic processes in the lungs and digestive organs, skin, chronic gastritis with secretory , gallstone disease, chronic pyelonephritis, prostate adenoma, diabetes mellitus, osteochondrosis of the spine, arthrosis, often (up to 10% of elderly people) depression, eye diseases (cataracts, glaucoma), hearing loss (as a result of auditory neuritis or otosclerosis), etc. ...

Diagnosis and analysis of combined pathology require a doctor to have a wide range of knowledge and not only age-related changes in organs and systems, but also symptoms of some diseases of the nervous system, musculoskeletal system, urogenital system, peculiarities of the course of surgical diseases, oncological alertness, etc.

Features of the clinical course of diseases. Elderly and old people can suffer from illnesses that have arisen at a young or mature age. Mainly, this refers to some inflammatory, metabolic processes, persistent functional disorders with a long-term chronic course. Like young people, they can develop acute, including infectious, diseases. However, the age-related characteristics of the body cause significant deviations in the course of these diseases. The most characteristic atypicality, unresponsiveness, smoothness clinical manifestations of diseases.

The old man has a tendency to slowly
growing pathological processes, at the age of 40–45, the process of "accumulation" of diseases is already taking place. In old and especially senile age, the morbidity structure changes significantly due to a decrease in the number of acute diseases and an increase in the number of diseases associated with the progression of chronic pathological diseases. Clinical observations of the features of the development and course of diseases in people of older age groups indicate that long-established diagnostic schemes for many
internal (and oncological) diseases are not applicable in geriatric practice. Diagnosis, like therapy, in older people requires a different approach than in younger people. This is due to a number of reasons: a) a slower and often disguised course of neoplastic processes in internal organs, pneumonia, myocardial infarction, pulmonary tuberculosis, diabetes mellitus, which is closely associated with the development of atherosclerosis and its complications; b) a different genesis and course of stomach ulcers developing on the basis of atherosclerosis; c) the influence of clinically pronounced age-related processes in the bones and joints of the spine, causing both circulatory disorders in a number of major vessels, and special symptoms, which are often the cause of erroneous diagnostics of heart diseases; d) the latent course of catastrophes in the abdominal cavity, requiring urgent surgical intervention.

Among the reasons are many other features of the course of acute diseases, caused by new properties of the aging human body, changes in its protective, including immune responses. Acute illnesses often become subchronic; the severity of the damage to the body does not correspond to the mild symptomatology of the disease.

When observing elderly and senile patients,
In assessing their condition and carrying out diagnostics, it is necessary to take into account not only the degree of deviation from the age indicators of the norm, but also the heterogeneity of the degree and rate of development of involution, degenerative-dystrophic processes, which is usually observed with premature aging, and the emergence of new qualities of adaptive mechanisms in various systems of the body. The cardiovascular system is primarily subject to changes; aging of the digestive system occurs at the slowest pace.

It is necessary to strictly distinguish between the concepts of aging and old age, cause and effect.

Old age - the naturally coming final period of age development.

Aging- a destructive process that develops as a result of the damaging action of exogenous and endogenous factors that increases with age, leading to insufficiency
physiological functions of the body. Aging leads to a limitation of the body's adaptive capabilities, a decrease in its reliability, and the development of age-related pathology. The participation of environmental factors in the development of aging justifies the search for an optimal lifestyle, environmental conditions that help slow the rate of aging. Environmental factors, affecting biological processes, affect life expectancy. The time of the onset of old age. Age periods do not have sharp boundaries. Along with the increase in life expectancy, ideas about the time of the onset of old age have changed.
So, the average life expectancy in ancient Rome was 28-30 years, so 40-year-old people were considered old people, and 60-year-olds - Deponentines, suitable only for sacrifices. In accordance with the WHO classification, the age of 45-59 years is considered average, 60-74 years old, people aged 75 and older are called old, and over
90 years old - long-livers.

1 What is old age and aging? Their fundamental difference.

2 What processes are characteristic of old age?

3 Historical aspects of assessing the views of the population on old age.

Lecture number 3

Aging and the sequence of ontogenetic processes. Constitutional features, belonging to a certain ecological-population group, the influence of social factors. The biological age of men and women.

There is a deep-rooted perception in public opinion of the earlier and faster aging of women. This is reflected in the preferences that are usually given to those marriages when the groom is older than the bride, but not vice versa. However, two phenomena that do not completely coincide with each other are confused here. According to biological processes, according to gerontologists, women age more slowly and live 6–8 years longer. For example, similar changes in the tissues of old women and men occur in the latter eight years earlier, that is, biological aging of women occurs later. The great vitality of women persists throughout their lives. Initially, more male embryos are laid, and during the first years of life and even the second or third decades, some predominance of men may persist, but by the end of the third decade, the numbers of both sexes are almost equal, and further the numerical predominance of women is increasing at an increasing rate. Among centenarians at the age of 100, this ratio is approximately three to four women per man. Probably, a certain role can be played by the protective function of female sex hormones - estrogens, which have an anti-sclerotic effect, and the general greater resistance of the female body as an adaptation to increased biological stress during childbirth. After menopause, atherosclerosis develops faster in women.

On the other hand, as already mentioned, women have more
fertility ceases early and abruptly. This is also a kind of adaptation, protection of the aging organism from the already unbearable load associated with pregnancy and childbirth. Female wilting is often accompanied by "masculinization": coarsening of the voice, facial features, changes in figure, gait, gestures, the appearance of facial hair (on the chin, upper lip), a tendency to baldness.

However, these processes are by no means mandatory and can vary greatly from person to person. Usually in healthy women, menopause is painless, although there may be circulatory disorders ("hot flashes") and some diseases. It is on these phenomena that the concept of an earlier aging of women is based, although, as we have seen, it is not quite adequate to general aging, reflecting simply an earlier “fading” of women, often associated with a loss of sexual attractiveness.

Similar information.

11 July 2008

Aging mechanisms are quite complex and diverse. Today there are several alternative theories that partly contradict each other and partly complement each other. Modern biology pays great attention to the problem of aging, and every year new facts appear that allow a deeper understanding of the mechanisms of this process.

MOLECULAR GENETIC THEORIES

The hypothesis that the cause of aging is changes in the genetic apparatus of the cell is one of the most recognized in modern gerontology.

Molecular genetic theories are divided into two large groups. Some scientists consider age-related changes in the genome as hereditarily programmed. Others believe that aging is the result of the accumulation of random mutations. Hence it follows that the aging process can be either a natural result of the growth and development of an organism, or a consequence of the accumulation of random errors in the system of storage and transmission of genetic information.

Telomeric theory

In 1961, the American gerontologist L. Hayflick established that human fibroblasts - skin cells capable of division - "in a test tube" can divide no more than 50 times. In honor of the discoverer, this phenomenon was called the "Hayflick limit." However, Hayflick offered no explanation for this phenomenon. In 1971, a researcher at the Institute of Biochemical Physics of the Russian Academy of Sciences A.M. Olovnikov, using data on the principles of DNA synthesis in cells, proposed a hypothesis according to which the "Hayflick limit" is explained by the fact that with each cell division the chromosomes are slightly shortened. Chromosomes have special end regions - telomeres, which after each doubling of chromosomes become a little shorter, and at some point are shortened so much that the cell can no longer divide. Then it gradually loses its vitality - this is precisely what, according to the telomere theory, is the aging of cells. The discovery in 1985 of the telomerase enzyme, which completes the construction of shortened telomeres in germ cells and tumor cells, ensuring their immortality, was a brilliant confirmation of Olovnikov's theory. True, the limit of 50-60 divisions is not valid for all cells: cancer and stem cells can theoretically divide indefinitely; in a living organism, stem cells can divide not tens, but thousands of times, but the connection between cell aging and telomere shortening is generally recognized. It is curious that the author himself recently decided that the telomere hypothesis does not explain the causes of aging, and first put forward one more, redusomal, and then a second, no less fantastic one - lunar gravity. Both have received neither experimental confirmation nor peer approval.

Elevational (ontogenetic) theory of aging

In the early 1950s, the well-known Russian gerontologist V.M. Dilman put forward and substantiated the idea of the existence of a single regulatory mechanism that determines the patterns of age-related changes in various homeostatic (maintaining the constancy of the internal environment) systems of the body. According to Dilman's hypothesis, the main link in the mechanisms of both development (lat. Elevatio - rise, in a figurative sense - development) and subsequent aging of the body is the hypothalamus - the "conductor" of the endocrine system. The main reason for aging is an age-related decrease in the sensitivity of the hypothalamus to regulatory signals from the nervous system and endocrine glands. Throughout the 1960s and 80s. with the help of experimental studies and clinical observations, it was found that it is this process that leads to age-related changes in the functions of the reproductive system and the hypothalamic-pituitary-adrenal system, which provides the necessary level of glucocorticoids produced by the adrenal cortex - "stress hormones", daily fluctuations in their concentration and increased secretion during stress, and, ultimately, to the development of the state of the so-called "hyperadaptosis".
According to Dilman's concept, aging and related diseases are a by-product of the implementation of the genetic program of ontogenesis - the development of an organism. The ontogenetic model of age-related pathology has opened up new approaches to the prevention of premature aging and age-related diseases that are the main causes of human death: heart disease, malignant neoplasms, strokes, metabolic immunosuppression, atherosclerosis, diabetes mellitus of the elderly and obesity, mental depression, autoimmune and some others. diseases. From the ontogenetic model it follows that the development of diseases and natural senile changes can be slowed down if the state of homeostasis is stabilized at the level reached by the end of the development of the organism. If we slow down the aging rate, then, as V.M. Dilman, it is possible to increase the species limits of human life.

Adaptive regulatory theory

The aging model developed by the outstanding Ukrainian physiologist and gerontologist V.V. Frolkis in the 1960s and 1970s, is based on the widespread belief that old age and death are genetically programmed. The "highlight" of Frolkis's theory is that age-related development and life expectancy are determined by the balance of two processes: along with the destructive process of aging, the process of "anti-aging" unfolds, for which Frolkis proposed the term "vitaukt" (Latin vita - life, auctum - to increase) ... This process is aimed at maintaining the vitality of the organism, its adaptation, and increasing life expectancy. The concept of anti-aging (vytaukte) has become widespread. Thus, in 1995, the first international congress on this problem was held in the United States.

An essential component of Frolkis's theory is the gene-regulatory hypothesis developed by him, according to which the primary mechanisms of aging are disturbances in the functioning of regulatory genes that control the activity of structural genes and, as a result, the intensity of synthesis of proteins encoded in them. Age-related disorders of gene regulation can lead not only to a change in the ratio of synthesized proteins, but also to the expression of previously inoperative genes, the appearance of previously not synthesized proteins, and, as a result, to aging and cell death.

V.V. Frolkis believed that the gene-regulatory mechanisms of aging are the basis for the development of common types of age-related pathology - atherosclerosis, cancer, diabetes, Parkinson's and Alzheimer's diseases. Depending on the activation or suppression of the functions of certain genes, this or that aging syndrome, this or that pathology will develop. On the basis of these ideas, the idea of gene-regulatory therapy was put forward, designed to prevent the shifts underlying the development of age-related pathology.

STOCHASTIC (PROBABILITY) THEORIES

According to this group of theories, aging is the result of random processes at the molecular level. We talked about this above: many researchers believe that aging is a consequence of the accumulation of random mutations in chromosomes as a result of the wear of DNA repair mechanisms - the correction of errors during its copying during cell division.

Free radical theory

Almost simultaneously put forward by D. Harman (1956) and N.M. Emanuel (1958), the free radical theory explains not only the mechanism of aging, but also a wide range of associated pathological processes (cardiovascular diseases, weakening of immunity, impaired brain function, cataracts , cancer and some others). According to this theory, the cause of cell dysfunction is the free radicals necessary for many biochemical processes - reactive oxygen species synthesized mainly in mitochondria - the energy factories of cells.

If a very aggressive, reactive free radical accidentally leaves the place where it is needed, it can damage DNA, RNA, proteins and lipids. Nature has provided a mechanism for protection against excess free radicals: in addition to superoxide dismutase and some other enzymes synthesized in mitochondria and cells, many substances that enter the body with food have an antioxidant effect, incl. vitamins A, C and E. Regular consumption of vegetables and fruits and even a few cups of tea or coffee a day will provide you with an adequate dose of polyphenols, which are also good antioxidants. Unfortunately, an excess of antioxidants - for example, with an overdose of dietary supplements - is not only unhealthy, but can even intensify oxidative processes in cells.

Aging is a mistake

The hypothesis of "aging by mistake" was put forward in 1954 by the American physicist M. Szilard. Investigating the effects of radiation on living organisms, he showed that the effect of ionizing radiation significantly reduces the lifespan of people and animals. Radiation causes numerous mutations in the DNA molecule and initiates some of the symptoms of aging, such as gray hair or cancers. From his observations, Szilard concluded that mutations are the direct cause of aging in living organisms. However, he did not explain the fact of aging of people and animals that were not exposed to radiation.

His follower L. Orgel believed that mutations in the genetic apparatus of a cell can be either spontaneous or arise in response to aggressive factors - ionizing radiation, ultraviolet radiation, exposure to viruses and toxic (mutagenic) substances, etc. Over time, the DNA repair system wears out, resulting in aging of the body.

Apoptosis (cell suicide) theory

Academician V.P. Skulachev calls his theory the theory of cellular apoptosis. Apoptosis (Greek "leaf fall") is a process of programmed cell death. As trees get rid of parts in order to preserve the whole, so each individual cell, having passed its life cycle, must die out and a new one must take its place. If a cell becomes infected with a virus, or a mutation occurs in it, leading to malignancy, or simply expires, then, in order not to endanger the entire organism, it must die. Unlike necrosis - the violent death of cells due to trauma, burns, poisoning, lack of oxygen as a result of clogging of blood vessels, etc., with apoptosis, the cell neatly disassembles itself, and neighboring cells use its fragments as a building material.
Mitochondria also undergo self-liquidation - having studied this process, Skulachev called it mitoptosis. Mitoptosis occurs when too many free radicals are produced in the mitochondria. When the number of dead mitochondria is too large, their decay products poison the cell and lead to its apoptosis. Aging, from the point of view of Skulachev, is the result of the fact that more cells die in the body than are born, and the dying functional cells are replaced by connective tissue. The essence of his work is the search for methods to counteract the destruction of cellular structures by free radicals. According to the scientist, old age is a disease that can and should be treated, the aging program of the body can be disabled and thereby turn off the mechanism that shortens our life.

According to Skulachev, the main reactive oxygen species leading to the death of mitochondria and cells is hydrogen peroxide. He is currently testing SKQ, a drug designed to prevent signs of aging.

Currently, there are many theories of aging, most of which consider the actual mechanisms of aging - these are, first of all, the theory of oxidative damage (Harman, 1987; Sohal, Weindruch, 1996) and the telomeric theory - (Slovnikov A.M., 1971, Hayflick, 1998). While revealing the underlying mechanisms of aging, these theories, nevertheless, do not establish direct limits of life expectancy (LB), since they do not determine the rate at which these mechanisms unfold and, thus, how fast the aging process proceeds. Another part of the theory is devoted to the development of aging in time, primarily the theory of the rate of life (TTZh - Pearl, 1928, Sohal, 1986; Lints, 1989).

In recent years, the theory of oxidative damage has increasingly been used as a concept that most adequately reflects the accumulated stock of knowledge about the mechanisms of aging (Harman, 1987; Fleming et ai, 1992; Sohal, Weindruch, 1996; Orr, 1996; Zhizhina and Blukhterova, 1999) ... This theory argues that the cause of aging is the production of oxidants that damage the structures of the body, and “the lifespan of organisms with the same metabolic rate should correlate with the level of their antioxidant protection” (Fleming et al, 1992). Currently, a close relationship has been established between TTZ and the theory of oxidative damage: "The theory of the rate of life in aging can be expressed as a theory of free radicals, based on the fact that free radicals arise as a normal metabolic product" (Parsons, 1996).

All modern theories of aging in one way or another are associated with the concept of homeostasis of the body. Genetic studies have revealed deep connections between lifespan and the body's abilities (Tatar, 1999). In theoretical gerontology, the concept of homeostasis is viewed in a broader context than in its classical understanding (Arking, 1991; Holliday, 1995). In physiology, homeostasis is considered as maintaining the constancy of the chemical composition of body fluids (Cannon, 1932; Sarkisov, 1981; Novoseltsev, 1978). Physiological mechanisms of homeostasis provide for this delivery of oxygen (blood circulation, respiration) and nutrients (digestive system), as well as the elimination of waste products (excretory systems). For gerontology, of interest is the constancy of cellular structures - somatic homeostasis, which is maintained by molecular genetic and cellular mechanisms (Sohal, Weindruch, 1996; Tatar, 1999).

Physiological mechanisms of homeostasis work on a faster time scale than somatic ones, which is a cardinally important fact for theoretical gerontology. In humans, a fast time scale covers a range from several seconds to several hours (for example, in this range, sequential mechanisms in the circulatory system are activated - Guyton, 1982). The slow time scale reflects age-related changes in the somatic mechanisms of homeostasis (Comfort, 1967; Frolkis, Muradyan, 1992).

An important aspect of the homeostatic approach to aging is the concept of natural death as “death from old age”. “The medical model of disease ... assumes that death is always the result of the development of the disease; if there were no disease, there would be no death ”(Fries, 1980; Hyflik, 1998). In fact, from a certain age, the body's ability to maintain homeostasis decreases, and at some point, even weak disturbances make its recovery impossible. “The inevitable result is natural death, occurring even without illness” (Fries, 1980, p. 131). However, natural death from old age as a result of depletion of homeostatic resources becomes a noticeable cause of death only when individuals are completely protected from environmental influences. Today, this is true only for experimental populations of animals, in particular, insects.

Based on the modern version of the theory of the rate of life, a homeostatic model of aging has been developed, in which physiological aging is associated with the accumulation of oxidative damage in the body within the framework of general biological concepts of the body's homeostasis (Novoseltsev et al., 1997, Novoseltsev et al, 2000)

An adult insect enters the life cycle with homeostatic mechanisms (their power So is determined by the genotype) and the antioxidant defense mechanism (the body's susceptibility to the action of oxidants is also determined by its genotype, which sets the age pattern of its “oxidative vulnerability” B.

Life processes are associated with oxygen consumption (the rate of consumption of which is described by the time pattern Wz). In proportion to the oxygen consumption in the body, oxidants are produced and oxidative damage accumulates, which leads to an age-related decrease in the value of S. As a result, oxygen delivery to the body gradually decreases, and the current quasi-stationary oxygen level, indicated by the X symbol, slowly decreases, at some age falling to the maximum permissible level XD Upon reaching this level, death occurs.

Thus, aging is presented as an age-related decrease in the homeostatic abilities of the body, and the rate of aging is determined by two factors - the rate of oxygen consumption (with a side effect in the form of the production of oxidants) and the effectiveness of antioxidant protection.

2 BASIC MODERN THEORY OF AGING IN A LIVING ORGANISM

All theories of aging can be roughly divided into two large groups: evolutionary theories and theories based on accidental cell damage. The former believe that aging is not a necessary property of living organisms, but a programmed process. According to them, aging has developed as a result of evolution due to some of the benefits that it gives to the entire population. In contrast, damage theories suggest that aging is the result of a natural process of accumulation of damage over time that the body tries to combat, and that differences in aging among organisms are the result of different effectiveness of this struggle. The latter approach is now considered established in the biology of aging. However, some researchers still defend the evolutionary approach, and some others completely ignore the division into evolutionary and damage theories. The latter statement is partly the result of a change in terminology: in some recent work, the term "evolutionary theories" refers not to "programmed aging" theories, which suggest the evolutionary emergence of aging as a beneficial phenomenon, but to an approach that describes why organisms should age, as opposed to the question of biochemical and physiological bases of aging. The hormonal-genetic approach is that in the process of a person's life, starting from birth, there is an increase in the sensitivity threshold of the hypothalamus, which ultimately after 40 years leads to hormonal imbalance and progressive disruption of all types of metabolism, including hypercholesterolemia. Therefore, the treatment of diseases of old age it is necessary to start with improving the sensitivity of the hypothalamus.

The theory of apoptosis (cell suicide). Academician V.P. Skulachev calls his theory the theory of cellular apoptosis. Apoptosis (Greek "leaf fall") is a process of programmed cell death. As trees get rid of parts in order to preserve the whole, so each individual cell, having passed its life cycle, must die out and a new one must take its place. If a cell becomes infected with a virus, or a mutation occurs in it, leading to malignancy, or simply expires, then, in order not to endanger the entire organism, it must die. Unlike necrosis - the violent death of cells due to trauma, burns, poisoning, lack of oxygen as a result of clogging of blood vessels, etc., with apoptosis, the cell neatly disassembles itself, and neighboring cells use its fragments as a building material.
Mitochondria also undergo self-liquidation - having studied this process, Skulachev called it mitoptosis. Mitoptosis occurs when too many free radicals are produced in the mitochondria. When the number of dead mitochondria is too large, their decay products poison the cell and lead to its apoptosis. Aging, from the point of view of Skulachev, is the result of the fact that more cells die in the body than are born, and the dying functional cells are replaced by connective tissue. The essence of his work is the search for methods to counteract the destruction of cellular structures by free radicals. According to the scientist, old age is a disease that can and should be treated, the aging program of the body can be disabled and thereby turn off the mechanism that shortens our life.

According to Skulachev, the main reactive oxygen species leading to the death of mitochondria and cells is hydrogen peroxide. He is currently testing SKQ, a drug designed to prevent signs of aging.

Free radical theory. Almost simultaneously put forward by D. Harman (1956) and N.M. Emanuel (1958), the free radical theory explains not only the mechanism of aging, but also a wide range of associated pathological processes (cardiovascular diseases, weakening of immunity, impaired brain function, cataracts , cancer and some others). According to this theory, the cause of cell dysfunction is the free radicals necessary for many biochemical processes - reactive oxygen species synthesized mainly in mitochondria - the energy factories of cells.

Adaptive and regulatory theory. The aging model developed by the outstanding Ukrainian physiologist and gerontologist V.V. Frolkis in the 1960s and 1970s, is based on the widespread belief that old age and death are genetically programmed. The "highlight" of Frolkis's theory is that age-related development and life expectancy are determined by the balance of two processes: along with the destructive process of aging, the process of "anti-aging" unfolds, for which Frolkis proposed the term "vitaukt" (Latin vita - life, auctum - to increase) ... This process is aimed at maintaining the vitality of the organism, its adaptation, and increasing life expectancy. The concept of anti-aging (vytaukte) has become widespread. Thus, in 1995, the first international congress on this problem was held in the United States.

Telomeric theory. In 1961, the American gerontologist L. Hayflick established that human fibroblasts - skin cells capable of division - "in a test tube" can divide no more than 50 times. In honor of the discoverer, this phenomenon was called the "Hayflick limit." However, Hayflick offered no explanation for this phenomenon. In 1971, a researcher at the Institute of Biochemical Physics of the Russian Academy of Sciences A.M. Olovnikov, using data on the principles of DNA synthesis in cells, proposed a hypothesis according to which the "Hayflick limit" is explained by the fact that with each cell division the chromosomes are slightly shortened. Chromosomes have special end regions - telomeres, which after each doubling of chromosomes become a little shorter, and at some point are shortened so much that the cell can no longer divide. Then it gradually loses its vitality - this is precisely what, according to the telomere theory, is the aging of cells. The discovery in 1985 of the telomerase enzyme, which completes the construction of shortened telomeres in germ cells and tumor cells, ensuring their immortality, was a brilliant confirmation of Olovnikov's theory. True, the limit of 50-60 divisions is not valid for all cells: cancer and stem cells can theoretically divide indefinitely; in a living organism, stem cells can divide not tens, but thousands of times, but the connection between cell aging and telomere shortening is generally recognized. It is curious that the author himself recently decided that the telomere hypothesis does not explain the causes of aging, and first put forward one more, redusomal, and then a second, no less fantastic one - lunar gravity. Both have received neither experimental confirmation nor peer approval.

Elevational (ontogenetic) theory of aging. In the early 1950s, the well-known Russian gerontologist V.M. Dilman put forward and substantiated the idea of the existence of a single regulatory mechanism that determines the patterns of age-related changes in various homeostatic (maintaining the constancy of the internal environment) systems of the body. According to Dilman's hypothesis, the main link in the mechanisms of both development (lat. Elevatio - rise, in a figurative sense - development) and subsequent aging of the body is the hypothalamus - the "conductor" of the endocrine system. The main reason for aging is an age-related decrease in the sensitivity of the hypothalamus to regulatory signals from the nervous system and endocrine glands. Throughout the 1960s and 80s. with the help of experimental studies and clinical observations, it was found that it is this process that leads to age-related changes in the functions of the reproductive system and the hypothalamic-pituitary-adrenal system, which provides the necessary level of glucocorticoids produced by the adrenal cortex - "stress hormones", daily fluctuations in their concentration and increased secretion during stress, and, ultimately, to the development of the state of the so-called "hyperadaptosis".

According to Dilman's concept, aging and related diseases are a by-product of the implementation of the genetic program of ontogenesis - the development of an organism. The ontogenetic model of age-related pathology has opened up new approaches to the prevention of premature aging and age-related diseases that are the main causes of human death: heart disease, malignant neoplasms, strokes, metabolic immunosuppression, atherosclerosis, diabetes mellitus of the elderly and obesity, mental depression, autoimmune and some others. diseases. From the ontogenetic model it follows that the development of diseases and natural senile changes can be slowed down if the state of homeostasis is stabilized at the level reached by the end of the development of the organism. If we slow down the aging rate, then, as V.M. Dilman, it is possible to increase the species limits of human life.

Mutation accumulation theory(English Mutations accumulation theory) - an evolutionary-genetic theory of the origin of aging, proposed by Peter Medawar in 1952. This theory views aging as a by-product of natural selection (as well as, for example, the evolutionary explanation for the development of blindness in cave and underground animals).

The probability of an individual's reproduction depends on his age, increasing from zero at the time of birth, and reaching a peak in young adult organisms (immediately after reaching puberty), after which it decreases due to an increase in the probability of death from external (predators, diseases, accidents) and internal (aging) reasons. At the same time, in natural conditions, organisms very rarely live up to the age when aging becomes noticeable, that is, mortality almost exclusively depends on external causes, for which aging has no effect. Harmful mutations in alleles that appear at a young age are thus subject to very strong evolutionary pressures, as they have a strong influence on the likelihood of reproduction. On the other hand, harmful mutations that appear late in life, at an age to which most of the population does not survive, will experience significantly less evolutionary pressure, because their carriers have already passed on their genes to the next generation and a decrease in the number of heirs due to these mutations insignificantly.

Mutations can affect the success of an organism both directly and indirectly. For example, a hypothetical mutation that increases the risk of fractures due to decreased calcium fixation is less deleterious than a mutation that affects the eggs in the uterus. From the point of view of evolution, it does not matter why the ability of an organism to reproduce is reduced. It is important that individuals who carry a deleterious mutation are less likely to reproduce if the deleterious effect of that mutation manifests itself earlier in life. For example, people with progeria (a genetic disease with symptoms of premature aging) live only 15-20 years, and practically cannot pass on their mutant genes to the next generation (considering the mutation to be dominant). In such conditions, progeria arises only as a result of new mutations, and not from the genes of the parents. In contrast, people with another genetic disease, Alzheimer's disease, which manifests itself late, have time to leave offspring before its onset. Thus, the disease is passed on to new generations and is accidental. In other words, the theory of accumulation of mutations envisages an increase with age in the frequency of genetic mutations that remain in the gene pool.

Mutation accumulation theory allows researchers to make several testable predictions. In particular, this theory provides that the dependence of the maximum life span of the offspring population on the maximum life span of the maternal organism should not be linear, as is observed for almost any other quantitative trait, which demonstrates heredity (for example, body height). This means that this relationship must have an unusual non-linear form, with an increasing slope for the dependence of the offspring's range of life on maternal life expectancy among longer-lived parents. This prediction follows directly from the key statement of the theory that the equilibrium frequency of genes, where a harmful mutation is possible, should increase with age due to weak evolutionary pressure against these mutations (Equilibrium gene frequency means the time independent frequency of genes that determines the balance between the occurrence of mutations and evolutionary pressure against them).

According to the theory of accumulation of mutations, genetic changes in maximum life expectancy are expected to increase with age. Thus, in a heterogeneous population, the same change in phenotype corresponds to a large number of changes in the genotype. The envisaged increase in additive genetic variation can be detected by studying the ratio of genetic changes under the condition of similar phenotypic changes. This ratio, the so-called heredity of life expectancy in the narrow sense, can be estimated as a doubled slope of the regression line depending on the life expectancy of offspring on the maternal life expectancy. Therefore, if age at death is indeed determined by the accumulation of deleterious delayed mutations, this slope is expected to become steeper with increasing maternal age at death. This prognosis was verified by an analysis of the genealogical data of heredity in European royalty and noble families, which are very well documented. It was found that the slope of the regression line of offspring does increase with the maximum age of the ancestors, as anticipated by the theory of accumulation of mutations. Similar results were obtained from studies of other model organisms, for example, the fruit fly Drosophila melanogaster

Today, however, the theory of the accumulation of mutations has not been confirmed by the example of specific genes and remains a hypothesis that requires further confirmation.

Disposable soma theory, sometimes the theory of the expendable soma (English Disposable soma theory) is an evolutionary physiological model that tries to explain the evolutionary origin of the aging process. The theory was proposed in 1977 by Thomas Kirkwood, then a fellow at the British National Institute for Biological Standards and Control, in his review article. This theory asks how an organism should manage its resources (in the first version of the theory it was only about energy) between maintaining and repairing the soma and other functions necessary for survival. The need for a compromise in the use of these resources arises due to the limited resources and the need to choose the best way to use them.

This theory was proposed in an attempt to create an evolutionary framework for understanding the existence and variation in the aging process that is universal for all living organisms. It suggests that individuals should invest in maintaining and repairing their soma (peripheral parts of the body) in line with their expectations for future life expectancy and reproductive capacity. However, an individual's expectations of future livelihood prospects and the likelihood of reproduction are not constant. For different species, and sometimes even for different individuals within a species, it is therefore necessary to maintain your soma over different periods of time. The disposable catfish theory states that species and populations that, on average, have few external threats and a low breeding rate should invest much more in protecting their catfish than species and populations that expect short lifespan and rapid breeding. When organisms are placed in sheltered conditions and freed from natural selection, differences in catfish repair and maintenance manifest themselves as interspecies and interpopulation differences in aging rates and maximum lifespan.

The theory is supported by the result of observation of populations of wild animals in nature, which shows that the number and activity of predators influence the survival strategy of the population. For example, studies of guppy populations have shown the evolution of life span, which manifests itself very quickly in response to changes in mortality. Guppies that grow with increased mortality are smaller, grow faster, reproduce at an earlier age, and devote more resources to reproduction than guppies that live with low external mortality. In addition, it has been suggested that one of the reasons birds and bats live longer than terrestrial animals of similar size is that, by being able to fly, they have been relieved of much of the evolutionary pressure from predators that terrestrial animals experience. ... Another study that confirmed some of the foundations of the theory was carried out on two populations of Virginia possums. One population of possums found on Sapelo Island, Georgia has no natural land predators, while another, found on the mainland, is hunted by cougars, foxes, and red lynxes. As a result, it was found that the island population gives birth to fewer cubs than the continental group, and generally survives until the second breeding season, gaining a second breeding opportunity. Members of this group are smaller in size, have a 25% longer average life expectancy and 50% longer maximum life expectancy than the continental group.

It is important to note that since the disposable soma theory only considers the evolutionary aspects of aging, the relationship between consumption, reproduction, and aging is considered in terms of the end result rather than specific mechanisms. If an individual animal has the ability to reproduce, it cannot expect biological immortality, since it needs to maintain its soma only to such a level that the average individual within the population can survive not for the time required to obtain the required number of offspring. However, the lack of reproductive capacity can have a positive effect on aging and longevity. This does not mean there is a link between life expectancy, reproduction, catfish support and longevity, the disposable catfish theory only envisages a trade-off between catfish support and reproduction, mediated by the resource allocation process. The theory suggests two reasons for the change of organisms. First, an increase in anticipation of adult mortality should lead to a decrease in support for soma. If the body does not expect to live long, it has less need to defend itself. Second, an increase in anticipation of the rate of reproduction should lead to a decrease in the support of the soma, since individuals anticipate a shortage of the resources necessary for reproduction.

The disposable soma theory does not postulate any specific mechanisms for supporting the soma, and therefore is compatible with most mechanistic models of aging, such as the accumulation of somatic mutations, altered proteins, mitochondrial theory, free radical theory, etc. low mortality rates from external causes and low reproduction rates also have the best protection against oxidative stress and, as a result, protein mutations and damage. For example, DNA repair (repair) is much worse in rodents than in primates, and somatic cells of mice are significantly more sensitive to oxidative stress caused by chemical methods than cells of long-lived mammals. The epithelial cells of the kidneys of relatively long-lived birds are also more resistant to chemical and radiation damage than the corresponding cells of mice.

Overall, the disposable soma theory provides a useful evolutionary framework for understanding the aging process. A large body of indirect evidence supports this theory, but detailed experimental studies are still lacking.

Mitochondrial theory. The importance of the relationship between molecular stress and aging has been hypothesized based on observations of the effect of accumulation of mutations in mitochondrial DNA (mtDNA). These data were supported by the observation of an increase with age in the number of cells lacking cytochrome c oxidase (COX), which is associated with mtDNA mutations. Such cells often have disruptions in ATP production and cellular energy balance.

The theory of somatic mutations. Many studies have shown an increase with age in the number of somatic mutations and other forms of DNA damage, suggesting DNA repair (repair) as an important factor in supporting cell longevity. DNA damage is typical of cells, and is caused by factors such as hard radiation and reactive oxygen species, and therefore DNA integrity can only be maintained through repair mechanisms. Indeed, there is a relationship between longevity and DNA repair, as demonstrated by the enzyme poly-ADP-ribose-polymerase-1 (PARP-1), an important player in the cellular response to stress-induced DNA damage. Higher PARP-1 levels are associated with longer life expectancy.

Gompertz-Makeham mortality law(sometimes just Gompertz's Law, Gompertz Distribution) is a statistical distribution that describes the mortality of humans and most multiple animals. According to the Gompertz-Makeham law, mortality is the sum of the age-independent component (Makeham member) and the age-dependent component (Gompertz function), which increases exponentially with age and describes the aging of the organism. In protected environments where there are no external causes of death (in laboratory conditions, in zoos, or for humans in developed countries), the age-independent component often becomes small, and the formula is simplified to the Gompertz function. The distribution was obtained and published by actuary and mathematician Benjamin Gompertz in 1832.

According to the Gompertz-Makeham law, the probability of death in a fixed short period of time after reaching age x is:

p = a + bx,

where x is age,

p is the relative probability of death over a certain period of time,

a and b are coefficients.

Thus, the population size decreases with age at a double exponential rate:

s (x) = exp [- m (bx + c)].

The Gompertz-Makeham mortality law best describes the dynamics of human mortality in the age range of 30-80 years. In the area of greater age, mortality does not increase as quickly as provided by this mortality law.

Historically, human mortality until the 1950s was largely caused by the time-independent component of the law of mortality (the Makeham term or parameter), while the age-dependent component (Gompertz function) remained almost unchanged. After the 1950s, the picture changed, which led to a decrease in mortality at a later age and the so-called "derectangularization" (flattening) of the survival curve.

In terms of reliability theory, the Gompertz-Makeham mortality law is the law of failure, where the rate of risk is a combination of age-independent failures and failures associated with aging, with an exponential increase in the rate of these failures.

Gompertz's law is a special case of the Fisher-Tippett distribution for negative age.

Epigenetic theory of aging. Cells slowly lose markers of repressed chromatin over time, which may be associated with cell differentiation in the body. The loss of repression markers should sooner or later lead to derepression of dormant transposons, respectively, to an increase in the amount of DNA damage caused by them, followed by activation of the cellular DNA repair system. The latter, in addition to participating in DNA repair, also cause unauthorized recombinations in telomeres. It is also possible that transposon recombinases can directly initiate such recombinations. As a result, extended sections of telomeric DNA are converted into rings and lost, and telomeres are shortened by the length of the lost circular DNA. This process accelerates the loss of telomeric DNA tens of times, and the subsequent apoptosis of most cells and predetermines aging as a biological phenomenon. The proposed theory is an alternative to the hypothesis of genetically programmed aging and the hypothesis of aging as a consequence of the accumulation of errors and damage, explains the mechanism of accelerating telomere loss in the case of oxidative stress and DNA damage, as well as the relationship between aging and the appearance of tumors.

Evolutionary genetic approach. The hypothesis that formed the basis of the genetic approach was proposed by Peter Medawar in 1952 and is now known as the "Mutations accumulation theory". Medawar noticed that animals in nature very rarely live to the age when aging becomes noticeable. According to his idea, alleles that appear during later periods of life and that arise as a result of mutations in germ cells are subject to rather weak evolutionary pressure, even if properties such as survival and reproduction are affected as a result of their action. Thus, these mutations can accumulate in the genome over many generations. However, any individual that has managed to avoid death for a long time experiences their effect, which manifests itself as aging. The same is true for animals in protected conditions.

Later, in 1957, D. Williams suggested the existence of pleiotropic genes that have different effects on the survival of organisms throughout different periods of life, that is, they are useful at a young age, when the effect of natural selection is strong, but harmful later, when the effect of natural selection is weak ... This idea is now known as “antagonistic pleiotropy”.

Together, these two theories form the basis of modern understanding of the genetics of aging. However, the identification of the responsible genes has had only limited success. The evidence for the accumulation of mutations remains controversial, while the evidence for the presence of pleiotropic genes is stronger, but they are not sufficiently substantiated. Examples of pleiotropic genes include the telomerase gene in eukaryotes and sigma factor-70 in bacteria. Although many genes are known that affect the lifespan of various organisms, no other clear example of pleiotropic genes has yet been found.

Evolutionary physiological approach. Antagonistic pleiotropy theory predicts that there must be genes with pleiotropic effects, the natural selection of which leads to aging. Several genes with pleiotropic effect at different stages of life have indeed been found - sigma-70 in E. coli, telomerase in eukaryotes, but no direct connection with aging has been shown, moreover it has not been shown that this is a typical phenomenon for all organisms, responsible for everything. aging effects. That is, these genes can only be considered as candidates for the role of genes predicted by theory. On the other hand, a number of physiological effects have been shown without identifying the genes responsible for them. Often we can talk about trade-offs similar to those predicted by antagonistic pleiotropy theory, without clearly defining the genes on which they depend. The physiological basis for such compromises is laid in the so-called Disposable Soma theory. This theory asks how an organism should manage its resources (in the first version of the theory it was only about energy) between maintaining and repairing the soma and other functions necessary for survival. The need for compromise arises from limited resources or the need to choose the best way to use them.

Body maintenance should only be done as much as necessary during normal survival time in nature. For example, since 90% of wild mice die during the first year of life, mainly from the cold, the investment of resources in survival over the long term will affect only 10% of the population. Thus, the three-year lifespan of mice is fully sufficient for all the needs in nature, and from an evolutionary point of view, resources should be spent, for example, on improving heat conservation or reproduction, instead of fighting old age. Thus, the lifespan of a mouse best suits the ecological conditions of its life.

The "disposable body" theory makes several assumptions that affect the physiologists of the aging process. According to this theory, aging results from imperfect repair and maintenance functions of somatic cells that are adapted to meet environmental needs. Damage, in turn, is the result of stochastic processes associated with the vital activity of cells. Longevity is controlled by controlling the genes that are responsible for these functions, and the immortality of generative cells, unlike somatic ones, is the result of a large expenditure of resources and, possibly, the absence of some sources of damage. OPARIN-HALDEN THEORY OF THE ORIGIN OF LIFE SYSTEM-STRUCTURAL ORGANIZATION AND SELF-ORGANIZATION IN LIVING NATURE Carbohydrates