Self-renewal of an organism at all its levels is not a sufficient anti-aging factor since the self-renewal process itself is not absolute and has the same random mechanisms.
Some obvious and experimentally and demographically confirmed conclusions are interesting, however, sometimes paradoxically sounding. So from the above, it is obvious that the greatest absolute decrease in viability can be observed at an early age, which we can see from the curves of changes in the ontogenesis of the absolute value of many physiological functions. This means that prevention of aging should begin at the earliest ages. At the same time, in old age, even small absolute changes in viability lead to pronounced changes in mortality, so at older ages, it is convenient to study the effects of adaptogens and biostimulants, although a small vital resource may not lead to a significant increase in life expectancy.
The mathematical analysis of the theories of aging, based on the modeling of its essence the age-related decline in overall viability, turned out to be surprisingly fruitful and suitable both for objectives of theoretical research and for practical research in population gerontology. At the same time, the common cause of aging is manifested by some general mechanisms that should be modeled and evaluated for their contribution to the overall aging of the system.
Another approach to the quantitative assessment of aging, based on the same definition reducing overall viability with age, is to consider the overall viability of the system as an integral of the viability of its parts, which, as applied to the body, means that the overall viability of the body consists of maintaining vitality (functional resource) of its main organs and systems (formula 5).
Х = k1 х1 + k2 х2 +.+kn хn (5)
where k is the coefficient, x1 n is the viability of organs and systems.
The definition of individual aging as a biological age is based on this.
2.4. Basic global mechanisms: types of aging
2.4.1. The main common mechanisms are types of aging
System analysis allows us to consider aging from several global points of view, thereby revealing the fundamental, general, global mechanisms or types of aging, as a reflection of fundamentally unidirectional common processes of aging.
Although the specific mechanisms of aging for different types of tissues and organisms can be quite different, all of them can be grouped into 2 groups that are essentially homogeneous according to the global mechanism, resulting from the global cause of aging the law of increasing entropy in some incompletely open systems, and also from counteraction by biological systems processes of regulation of growth and development of a biosystem.
Existing theories of aging focus on several hundred specific mechanisms of aging. However, attentive analysis of these mechanisms and essential modeling of the aging process ((Dontsov, 1990; 2011; 2017; Gompertz, 1825; Hayflick, 2007; Murphy, Partridge, 2008; Vern et al., 2009: van Leeuwen et al., 2010; Walker, 2011; Kirkwood, Melov, 2011; Masoro, Austad, 2011; Rando, Chang, 2012), as well as consideration of the aging phenomenon given in previous publications, allow us to group these mechanisms into a small number of classes general aging mechanisms and in general can only be theoretically reduced to stochastic and regulatory types of aging, while for biological systems the stochastic type appears as a probabilistic death of non-renewable elements, as well as a contamination of the system by external intoxes ikantami and internal metabolites.
Thus, if there is one common cause of aging, there are 2 types of aging and 3 main, fundamental mechanisms of aging.
2.4.2. Stochastic dependent death non-elements of the system
A fully formed organism has many non-updated elements at all its hierarchical levels: unique genes, non-dividing cells (for example, nerve cells, including autonomic control centers), non-regenerating structures of organs (alveoli, nephrons, etc.), organs themselves and etc.
The loss of these elements with age is probabilistic, and therefore in the simplest case, it is described by the same type of formula as the loss of overall viability:
dX / dt = -k * X,
where X is the number of non-updated elements of the body.
Graphs of total aging (mortality) for Gompertz and mortality associated with a decrease in viability due to the loss of non-renewable elements, therefore, should coincide and is exponent.
It is known that the loss of alveoli, nephrons with age, reaches 50%, and that of nerve cells in the hypothalamic regulatory centers 80% (which links this mechanism with the regulatory mechanism of aging). In nature, the stochastic mechanism of aging is fully realized in postmitotic animals (for example, in Drosophila), in which there are practically only non-updated structural units.
The death of elements is the extreme expression of the mechanism mentioned, which, in general terms, leads to changes in the elements of any system. With age, individual structures in the body can not only die, but also change due to accumulating micro- and macro- damage, or change the structure and function of adaptation.
Due to the non-ideal selection mechanisms and self-renewal of such structures in the body, these structures accumulate with age (increase in the number of old, incapacitated cells in all organs and tissues, degeneration, accumulation of mutations in the genome, decrease in the number and quality of sperm cells, accumulation of sclerotic elements in tissues, etc.); the functions of such structures are usually reduced. The accumulation of damaged elements is probabilistic in nature; therefore, the decrease in the number of normal, intact elements with age is described by the same type of formula as the Gompertz formula for loss of general viability.
The main role in the elimination of damage is played by the mechanism of cell division, therefore the deterioration of this process manifests itself morphologically in the form of a wide variety of tissue changes changes in the forms and sizes of subunits, atrophy, hypertrophy of functional tissue, replacement with nonfunctional connective tissue elements, etc. This is the basis of an increase in morphological (and functional) diversity at the tissue level observed with age and a decrease in their functions. This mechanism underlies such a typical aging phenomenon as atrophy of tissues consisting of constantly self-renewing cells (for example, skin).
2.4.3. Stochastic dependent cumulative mechanism of aging
The most common mechanism for confronting entropy is the flow of energy from the outside, which is carried out for all living organisms through the processes of nutrition and respiration metabolism. These processes cannot be perfect, therefore inevitably there should be production waste unworkable ballast molecules and harmful toxic substances, the removal of which from the body in principle cannot be 100% ideal process, as a result of which pollution inevitably accumulates in the body.
Harmful elements contained in food, in inhaled air, in information flows (exotoxins) also contribute to this process.
Harmful elements contained in food, in inhaled air, in information flows (exotoxins) also contribute to this process.
The result is age-accumulated pollution, by which it is generally necessary to understand the interfering, non-functional and toxic elements of different nature.
Examples of this mechanism can serve in the general case: toxins and heavy metals associated with tissues; scars from old wounds and inflammatory processes; chronic infections; cholesterol plaques on vessels; not functioning protein complexes in cells, lipofuscin in nerve cells, osteochondrosis phenomena; effects of mental injury, etc.
The change with age of the flow of matter and energy through the organisms can be estimated from the level of metabolism. It is known that basal metabolism decreases with the age of about 10%.
Apparently, this mechanism is not leading, it is possible, however, that it can make a significant contribution in the later stages of life.
This is known, for example, for beetles the accumulation of contaminations in the yellow body is critical for them at the end of life.
In humans, it is known to use enterosorbents in order to counteract this mechanism, which leads to an increase in real life expectancy of 57 years. Apparently, this is the real contribution of this mechanism to human aging.
Most importantly, the use of agents that oppose this mechanism seems to be for nerve cells, which in old age turn out to be filled with lymphuscin up to 70% of their volume. Centrofenoxin, which reduces its quantity, at the same time has a pronounced psychostimulating effect.
2.4.4. Regulatory aging
Growth and development are integral parts of life. The main mechanism of programmed regulation at the stage of organism formation is known: usually, a decrease in the function of suppressor cells leads to disinhibition of stimulating cells producing a regulatory factor. Nervous regulatory cells are concentrated primarily in the autonomic regulatory centers of the hypothalamus, in the nuclei of which the death of up to 80% of these cells is observed with age. The disinhibition of stimulating cells gives a constant growing gradient of a regulating factor with a maximum when the inhibitory population is completely disabled. Such a gradient, for example, of sex hormones (the final factors that realize the regulation for a given function) leads to the inclusion of puberty. If we assume that regulatory cells wear out with age, die in a random, probabilistic manner and do not resume, then it is easy to see that the age dynamics of these cells and the final regulatory factor can produce complex dynamics responsible for growth and development and for the subsequent period of aging.
We have proposed a general model of such regulation, which consists in disinhibition of stimulating cells when inhibiting death, which determines growth and development, but if death also affects stimulating regulatory cells, then over time the development program is depleted regulatory aging develops (Dontsov, 1990, 2011, 2017). Interestingly, this is essentially the only and very simple model that describes changes in viability (and mortality as a quantitative criterion of aging in general) during all periods of an organisms life. The latter suggests that regulatory mechanisms may play a crucial role in the aging process of the organism as a whole; while the remaining 3 common mechanisms of aging contribute to the last years of life and against the background of already developed pronounced regulatory changes.
Given the fact that the body has enough long-lived non-dividing nerve cells in other parts of the brain, we can speak about the fundamental possibility of a sharp slowdown in aging by replacing (transplant) quickly dying regulatory cells by long-lived or young, by reducing their death, pharmacologic stimulation, hypnosis, etc. Known since antiquity techniques of yoga, associated with psychopathy and activation of the lower-back parts of the brain.
Typical mechanisms of regulatory changes associated with aging in humans are the end of growth (growth hormone) and development (sex hormones, menopause), immunity involution (epiphys hormones), changes in the insular system (latent diabetes of the elderly), etc., however, the main question remains what is the main regulatory mechanism closely related to aging.
The most important mechanism to resist aging is, as noted above, cell division, which alone is capable of fully resisting all four common mechanisms of aging; its slowdown is critical for the manifestation of aging of self-renewing tissues, which are in the majority of mammals.
Therefore, the reduction of growth factors for self-renewing cells and the power of other regulatory systems of cell growth (including depletion and change in stem cell activity) is, in our opinion, the most important mechanism for the realization of aging in many species and in humans as well.
We have therefore developed an immuno-regulatory theory of aging (here theory is understood in the narrow sense as an important mechanism of aging), showing that age-related immune deficiency (as a result of central regulatory changes) affects the regulation of cellular growth of somatic tissues, being the most important mechanism for the aging of mammals in general and humans in particular (Dontsov, 1990, 2011, 2017).
In addition, regulatory mechanisms are important in connection with the end of growth and development programs, with which climax processes and associated osteoporosis are associated.
Replacement therapy with sex hormones, which was widely used at one time in developed countries, sharply reduced the severity of osteoporosis in women, alleviating the symptoms of menopause.
However, the side effects caused by the increased incidence of tumors led to the need to drastically limit such therapy.
This indicates that the body is aging as an integral system and influences individual mechanisms has either a small effect or even leads to pathology. Indeed, an increase in cell growth against the background of reduced immunity will only lead to an increase in the frequency of tumors.
2.4.5. The relationship of the main mechanisms of aging
The main mechanisms of aging, being the general directions for the implementation of a common single cause of aging, are already manifested by private mechanisms of aging, which can be grouped together according to similar mechanisms, representing general aging syndromes. The development of the syndrome itself in the body occurs according to general laws, regardless of the cause that caused them, therefore the syndromes that develop with aging are a convenient point of application of the effects of anti-aging agents.
Different mechanisms of aging are interconnected not only vertically, which realizes the common cause of aging depending on the specific conditions of its manifestation in various organs and tissues, but also horizontally among themselves.
So, all three main mechanisms of aging are related to each other, affecting each other in one degree or another.
Consideration of the biological meaning of the main mechanisms of aging leads to the obvious conclusion that the data of the mechanisms inevitably interact with each other in the whole organism they influence each other, interpenetrate each other:
pollution reduces the stability of the elements, increasing the likelihood of their damage and death, reduces the efficiency of functioning, including the elements of regulation in the neuro-vegetative centers;