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 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, 1990—2019).
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