The main scientific theories of aging

The mechanisms of aging are quite complex and diverse. Today there are several alternative theories that partly contradict each other, and partly complement each other. Modern biology pays a lot of 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 inherently programmed. Others believe that aging is the result of the accumulation of random mutations. It follows from this that the aging process can be either a natural result of the growth and development of the 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 vitro" can divide no more than 50 times. In honor of the discoverer, this phenomenon was called the "Hayflick limit". However, Hayflick did not offer any 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 sections – telomeres, which after each chromosome doubling become slightly shorter, and at some point shorten so much that the cell can no longer divide. Then it gradually loses viability – this, according to the telomeric theory, is the aging of cells. The discovery in 1985 of the telomerase enzyme, which completes 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 true 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 link between cell aging and telomere shortening is generally recognized. It is curious that the author himself recently decided that the telomeric hypothesis does not explain the causes of aging, and first put forward another, redusomal, and then the second, no less fantastic – moongravity. Both of them received neither experimental confirmation nor the approval of colleagues.

Elevation (ontogenetic) theory of aging

In the early 1950s, the famous 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 (Latin elevatio – rise, in a figurative sense – development) and subsequent aging of the body is the hypothalamus – the "conductor" of the endocrine system. The main cause of aging is an age–related decrease in the sensitivity of the hypothalamus to regulatory signals coming from the nervous system and the endocrine glands. During the 1960s-80s, with the help of experimental studies and clinical observations, it was found that this process 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, eventually, to the development of a state of 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 the 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 other diseases. It follows from the ontogenetic model 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 rate of aging, then, as V.M. Dilman believed, it is possible to increase the specific limits of human life.

Adaptive-regulatory theory

The model of aging developed by the outstanding Ukrainian physiologist and gerontologist V.V. Frolkis in the 1960s and 70s is based on the widespread notion that old age and death are genetically programmed. The "highlight" of Frolkis' theory is that age development and life expectancy are determined by the balance of two processes: along with the destructive aging process, the process of "anti-aging" is unfolding, for which Frolkis proposed the term "vitaukt" (Latin vita – life, auctum – to increase). This process is aimed at maintaining the viability of the organism, its adaptation, and increasing life expectancy. Ideas about anti-aging (vitaukt) have become widespread. So, in 1995, the first international congress on this problem was held in the USA.

An essential component of Frolkis' theory is the genoregulatory hypothesis developed by him, according to which the primary mechanisms of aging are disturbances in the work 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 inactive genes, the appearance of previously synthesized proteins and, as a result, to aging and cell death.

V.V.Frolkis believed that the genoregulatory 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, one or another aging syndrome, one or another pathology will develop. Based on these ideas, the idea of genoregulatory therapy was put forward, designed to prevent the shifts underlying the development of age-related pathology.

STOCHASTIC (PROBABILISTIC) 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 deterioration of DNA repair mechanisms – correcting errors when copying it during cell division.

Theory of free radicals

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 pathological processes associated with it (cardiovascular diseases, weakened immunity, brain function disorders, 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, chemically active free radical accidentally leaves the place where it is needed, it can damage DNA, RNA, proteins, and lipids. Nature has provided a mechanism of protection against excess free radicals: in addition to superoxide dismutase and some other enzymes synthesized in mitochondria and cells, many substances entering 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 a sufficient dose polyphenols, which are also good antioxidants. Unfortunately, an excess of antioxidants – for example, in case of an overdose of biologically active additives – is not only not useful, but can even enhance 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 shortens the life span of humans and animals. Under the influence of radiation, numerous mutations occur in the DNA molecule and some symptoms of aging, such as gray hair or cancerous tumors, are initiated. From his observations, Szilard concluded that mutations are the direct cause of aging of living organisms. However, he did not explain the fact of aging of people and animals who 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 the effects of 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.

Theory of apoptosis (cell suicide)

Academician V.P. Skulachev calls his theory the theory of cellular apoptosis. Apoptosis (Greek. "leaf fall") is the process of programmed cell death. Just as trees get rid of parts in order to preserve the whole, so each individual cell, having passed its life cycle, must die 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 its existence simply expires, then in order not to endanger the entire organism, it must die. Unlike necrosis – the violent death of cells due to injury, burn, poisoning, lack of oxygen as a result of clogging of blood vessels, etc., during apoptosis, the cell is carefully self-disassembled into parts, and neighboring cells use its fragments as a building material.
Mitochondria also undergo self–destruction - having studied this process, Skulachev called it mitoptosis. Mitoptosis occurs if too many free radicals are formed 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 Skulachev's point of view, 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 lives.

According to Skulachev, the main of the reactive oxygen species that lead to the death of mitochondria and cells is hydrogen peroxide. Currently, SKQ, a drug designed to prevent signs of aging, is being tested under his leadership.

Portal "Eternal youth" http://vechnayamolodost.ru 15.07.2009