General system theory of aging. Special role of the immune system

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 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;

– the death of elements reduces the cleaning efficiency (including from damaged elements) and the number of regulatory elements;

– regulation that stimulates proliferation and renewal is, in fact, the main mechanism resisting pollution (“diluting” with rapidly growing new bioplasm), death and damage (adaptive influences). At the same time, impaired regulation is critical for overall adaptability and resistance of the body during aging.

Note that in the final analysis, the most important is the stochastic mechanism of aging, which implements the main aging process – the damage and death of the main structural units of the body.

This scheme can be mathematically calculated and opens up possibilities for modeling and forecasting external influences on the main aging processes in an experiment.

Chapter 3. Modeling the phenomenon and mechanisms of aging

3.1. Mechanical model of system aging

3.1.1. An example of a mechanical model of aging systems

Aging is a common property of both living and non-living systems and is the wear, degradation, reduction of the order, structure, and function of a complex system. The aging phenomenon is easily amenable to theoretical analysis using modern scientific methodology – the theory of systems (Checkland, 1986; Nicolis, 1989; Prigogine, 1960, etc.).

The basic patterns and the very cause of aging are clearly seen in the example of a mechanical model, for which it suffices to take an auto-car as a specific example of a mechanical system. In this case, it is quite clear that the general reason for the system’s self-change from order to chaos is known; it is one – the natural direction of change sets the law of increasing entropy for naturally occurring reactions in nature for any systems.

This is the reason, as well as the main mechanism – the stochastic aging of the system.

Many different natural influences on such a mechanical system in a random way (guided by the law of increasing entropy) lead to the same thing – a decrease in its stability, order, an increase in chaos, that is, an aging system.

It is also easy to see on this model that the aging mechanisms of even such a simple system are multiple and probabilistic in nature: mechanical (tires, brakes), physical (metal fatigue), physical and chemical (burning out candles), chemical (rusting), biological (fungus), socio-psychological, etc.