The effect of reducing the aging rate (d (m)) for middle ages is accompanied by the phenomenon of inversion of the overall mortality rate (m) for ages of long-livers: the natural m decrease, observed for all countries in earlier historical periods, is replaced by an increase in modern times. However, in the d (m) charts, it can be seen that the decrease in the aging rate of the long-livers is preserved throughout all historical periods. The latter means that the phenomenon of mortality inversion is associated with the external influences on mortality, and not with a change in the aging rate at this time.
Ways to restore regulatory programs the most promising direction for the impact on aging.
The problem of recovery and correction of regulatory programs of the brain is central to age biology, since many body functions (sexual, immune, metabolic rate, total hormones and the balance of different types of hormones, nervous trophism, growth program, etc.) undergo drastic changes throughout life precisely because of the programmed changes in the regulatory centers, primarily at the level of the hypothalamus.
The methods of brain embryonic tissue transplantation developed in recent years make it possible to begin work on the restoration of depleted regulatory programs in old animals. The results indicate the fundamental possibility of restoring development programs lost or exhausted with age, as well as, possibly, imposing new programs (for example, during interspecific transplants) in order to influence the aging process in the right direction. An alternative to surgical intervention are the methods of pharmacological or physiotherapeutic activation of the corresponding nuclei of the hypothalamus, as well as the creation of new regulatory centers and pacemakers, including the use of psychotherapeutic techniques, hypnosis, etc.
The regulation of cellular growth at different levels of hierarchical structures of the body is essential for the integrity of the body.
The works of M. Eigen and P. Schuster show how different types of structures (cells) could be combined with their own regulation systems. According to the authors definition, a hypercycle is a principle of natural self-organization, causing integration and a coordinated evolution of a system of functionally related self-replicating units, uniting it into a single whole. The basis of the hypercycle theory is proof of the inevitability of the formation in the process of evolution of functional links of a higher order between self-replicating units systems of a lower order that are part of a single hypercycle system. With such a union, a self-regulating system of a higher order is formed, which preserves the constancy of the interrelationships within the incoming systems.
The 3 elements (regulated population, helper and suppressor populations) form an elementary self-regulating unit of 3 cell populations CELL HYPERCYCL: the population of somatic cells is regulated by stimulating (h) and inhibiting (s) regulatory populations.
Despite the simplicity of the description and great biological significance, the cell hypercycle is not given worthy attention in the literature, but the concept of a cell hypercycle means:
a new mechanism in evolution during the formation of multicellular organisms, which made possible the very existence of multi-cell as a whole;
a fundamentally new level of regulation of cell growth in the body (the level of cell populations), and, therefore, a new system in the body;
the presence of self-organization processes at this level;
the basis for the formation of higher levels of regulation (neuro-humoral) and their indirect effect on cell growth;
the basis for the formation of a special cellular system for regulating the growth of somatic cells in the organism a new system in the organism (Dontsov, 1986, 1987, 1989, 1990, 2009, 2011, 2017a, b), which in turn is the basis for the formation of special systems including including the immune system a new theory of the formation of immunity (Dontsov, 1989, 1990, 2011, 2017a, b),
as well as a new immune theory of aging as a depletion of the immunity system due to changes in regulatory systems (Dontsov, 1989, 1990, 2011a, b).
Thus, the self-organization of growing cell populations into a single mutually coordinated system is the central and initial moment of the formation of a cell regulation system at the level of interaction of different types of cell systems in the body..
Further development of the cell hypercycle in phylogenesis should have taken place according to general evolutionary laws the following biological phenomena can theoretically be predicted and experimentally observed:
increase the number of regulated units,
specialization of cell populations (the selection of somatic and regulatory populations);
specialization of regulatory populations, leading, for example, to the phenomenon of memory in the regeneration of organs and tissues, transferred by T-lymphocytes.
the emergence of functional regulation (the emergence of mechanisms Go/G1 transition and its regulation separately from the G1/S transition),
add-on regulation systems of the whole organism (for the regulation of growth and development).
In general, such a system is represented by a number of differentiated functional types of cells (skin, mucous membranes, liver, kidneys, etc.), which perform primarily their own type of functions. They are usually at rest, but when cells of a certain tissue are activated, they become G1 ready for cell division.
The somatic cells entering the cell cycle (G1) are regulated by both nonspecific and specific for this tissue regulating cells of the stimulating and inhibiting type, integrating various growing cells into a single system.
Already specialized cell regulators the Cells Regulators of Proliferation (CRP System), which themselves begin to activate and divide, react to this state, and also secrete growth factors for functional cell types, stimulating them to grow and divide.
In the course of growth and division of functional cell types, regulatory feedback cells are activated and their ratio to stimulating cell types determines the growth kinetics of functional tissue types. At the initial stages, nonspecific regulatory cells are activated, at later stages, specific CRP, which determine the effects of specific memory detected during repeated regeneration.
The participation of lymphocytes in the processes of regeneration and normal tissue growth was emphasized by a number of authors, and from the very beginning the immune system was assigned the role of integrative, preserving the whole organism. Immunomodulators have long been proposed as stimulators of regeneration processes, as well as the idea that regeneration and the immune system are interrelated (Babeva et al., 1982, 1987; Giełdanowski, 1983; Romanova, 1984), and all organs influence a single mechanism on the growth of all other organs (Romanova, 1984), which requires a special system of such interactions.
The lymphocyte transfer of regenerative information by lymphocytes from animals with liver regeneration was able to induce the proliferation and growth of liver cells during the syngeneic transfer to intact animals (Babaeva, 1995; Babaeva et al., 1979, 1982, 1987, 2007).
The lymphocyte transfer of regenerative information by lymphocytes from animals with liver regeneration was able to induce the proliferation and growth of liver cells during the syngeneic transfer to intact animals (Babaeva, 1995; Babaeva et al., 1979, 1982, 1987, 2007).
The transfer of a hyperplastic reaction by lymphocytes is possible, apparently, for any tissue and for any processes, for example, with isoproterenol-induced hypertrophy of the salivary glands of rodents (Dontsov, 1985, 1986), with functional hyperplasia of the heart (Svet-Moldavsky et al., 1974) and other processes, as well as in hypo-plastic reactions and pathological osteopetrosis.
The growth processes of the whole organism are also associated with the immune system. It has long been known that general growth retardation (dwarfism of mice) can be eliminated by transferring lymphocytes from healthy animals, and T-lymphocytes have receptors for the somatotropic hormone and somatostatin, the number of receptors is higher during the growth of animals, and the effect of the hormone appears only in the presence of thymus; somatotropic hormone stimulates the production of thymocyte in dogs and restores the formation of autologous rosettes with thymocytes in hypothyroid rats, while somatostatin inhibits lymphocyte proliferation (Martunenko, Shostak, 1982 Payan et al., 1984).
Based on the idea of the important regulatory role of T-lymphocytes in the cellular growth of somatic tissues, it can be assumed that the system of regulatory T-lymphocytes should arise very early in phylogenesis and be sufficiently complex to manage the various processes of tissue growth, as well as their integration into a single growing system in the process of ontogeny. Based on all the above facts, we have assumed that the function of regulating the cell growth of different somatic cells is phylogenetically more ancient and more important. Actually, this is the evolutionary force that forms the complex system of T-lymphocyte regulators of the proliferation of any cells, including T and B-effectors of immunity, which are phylogenetically later and simpler. In this case, the immune system is only a part of a more complex and general system for regulating the cellular growth the CRP system (Dontsov, 1989, 1990, 2011, 2011).
In particular, we have isolated and characterized such T-growth regulators of various somatic cells of the body, studied their kinetics, peculiarities of the phenotype, the reaction to some pharmacological agents, the selection of regulatory factors specific to somatic cells, etc. (Dontsov, 19902019).
Thus, it can be assumed that with aging, the function of T-lymphocytes of the CRP system decreases dramatically as a result of changes in the organism`s regulatory systems. We found a number of such data experimentally and showed the possibility of reactivation and rapid restoration of cell growth potential when exposed to the CRP-system cells (Dontsov, 1990, 2011).
The proposed new immune theory of aging, therefore, has not only theoretical interest but also allows you to use the full potential of immunopharmacology to counteract one of the most important mechanisms of aging the reduction of cellular self-renewal in mammals and humans with age.
We have shown the possibility of restoring the cell tissue growth potential that decreases with age under the influence of Transfer Factor, which gives the right to speak about the likelihood of TF influence on other manifestations of aging. It has been shown that TF is able to reduce biological age, assessed by a variety of parameters, in humans; and correct age-related immunodeficiency with increasing potential of cell growth.
Chapter 1. Methodology and principles of studying the aging phenomenon
1.1. The main methodological errors, myths, and cliches in the general analysis of the problem of aging
The most famous and common is, apparently, a statement from which often popular, and often scientific, lectures on aging often begin.
They say that the general theory of aging does not exist, there are several hundreds of theories of aging, but none of them is true, that you need to create a correct theory of aging, which will indicate the unknown cause of aging and abolish aging, leading not only to eternal youth but also to immortality.
In fact, everything here is not true exactly the opposite: the theory of aging exist, it is one, it includes all existing theories as special cases the mechanisms of aging, it is impossible to abolish aging as a general phenomenon of life, but also of Being as a whole, but eternal youth does not mean immortality.
The common cause of aging is known as part of ontogenesis, part of life itself, as a phenomenon of disruptions in the structure and function of the system accumulating with age, as movements from order to chaos (Comfort, 1967; Galimov, 2006; Giaimo, 2014; Gibbs, 1928; Gompertz, 1825; Gladyshev, 2012; Hayflick, 2007; Dontsov, 1990, 1998; Dontsov, Krutko, 2009, 2012, 2016; Krutko et al, 2018; Nicolis, 1989).
In general, it is a natural process in nature, since it proceeds with an increase in entropy; in a particular form, this is known as the second law of thermodynamics the accumulation of chaos in a discrete system.
But the reason is a principle, not a mechanism; it cannot be canceled (like most fundamental reasons); one can only oppose another principle (self-renewal and development).
The desired eternal youth would not lead to immortality, since aging is an increase in the probability of death with age, and eternal youth is only the constant (and not zero) probability of death throughout life. Such a situation would only lead to a different principle of extinction of the ever young population with a relatively small increase in Average life expectancy (ALE), but with a very large of psycho-social problems.
Indeed, during aging, when the probability of death increases with age by an order of magnitude, the main extinction of the population is drastically shifted to older ages, whereas with eternal youth the probability of death is constant throughout life and the average life expectancy (50% survival rate) sharply shifted to the left, which is typical of all systems with a constant stochastic loss of elements, for example, for the radioactive decay of elements.
From demographic data on mortality in developed countries, it is known that life expectancy in them now reaches 8085 years or more, that is, the population is guaranteed life expectancy, which is considered by the population as personally expected, guaranteed duration of their own lives, about 8590% of Maximum (90100 years).
On the other hand, the forever young ALE would not reach even 15% of the maximum possible life span, and the absolute values of the ALE are not important here since the fundamental mortality curve depends on the principle itself the immutability of mortality with age ((Figure 1)).
Figure 1. The probability of mortality of the population for an aging (left) and ageless (right) population. Horizontal time (years), vertical the percentage of survivors persons. Average life expectancy is indicated by the vertical dotted line on the horizontal time axis. The probability of mortality of the population: ageless population, for 20-year-olds 0.001% per year.