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.
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 5—7 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 organism’s 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