title: [Impairment of regeneration in aging: appropriateness or stochastics?].
abstract: There is a viewpoint that suppression of the proliferative capacity of cells and impairment of the regeneration of tissues and organs in aging are a consequence of specially arisen during evolution mechanisms that reduce the risk of malignant transformation and, thus, protect against cancer. At the same time, senescent cells of the body begin to accumulate a variety of macromolecular defects, which, conversely, increase the likelihood of their transformation into cancer cells. Thus, according to the point, the restriction of cell proliferation is a double-edged sword, which, on the one hand, reduces the likelihood of developing cancer at an early age, but on the other hand--limits life span due to the accumulation of "damaged" cells in old age. However, it remains unclear why normal human cells in vitro, with none of the mentioned "anticancer" barriers functioning at the organismal level only, NEVER undergo spontaneous malignant transformation. In addition, it is also unclear how the freshwater hydra which, under certain conditions, has really no postmitotic and senescent cells, escapes both aging and cancer and, at such conditions (excluding the need for sexual reproduction), can live almost indefinitely, having a great regenerative potential (new organism can arise even from a 1/100 of the old one). I believe that the restriction of cell proliferation in an aging multicellular organism is not a consequence of implementing a special program. Apparently, there is no special program of aging. It is only a "byproduct" of the program of development, implementation of which in higher organisms suggests the need for the emergence of cell populations with very low or even zero proliferative activity, which determines the limited capacity of relevant organs and tissues to regenerate. At the same time, it is the presence of highly differentiated cell populations, barely able or completely unable to reproduce (neurons, cardiomyocytes, hepatocytes), that ensures the normal functioning of the higher animals and humans. Even the regeneration of these organs with the help of stem cells could lead to a breach of the necessary interactions in complex systems. Reductionism in experimental-gerontological research ("everything is determined by deleterious changes in single cells") that has become widespread in recent decades, stimulated the emergence of a number of model systems for studying mechanisms of aging in isolated cells (Hayflick phenomenon, the model of "stationary phase aging", the cell-kinetic model for testing geroprotectors and geropromoters, etc.). However, at present it seems that the data obtained in such models cannot be automatically applied to the situation in the whole organism. Apparently, the impairment of regulatory processes, realized at the neurohumoral level, still plays the main role in the mechanisms of aging of multicellular organisms, not just the accumulation of macromolecular defects in individual cells. It is possible that it is the deterioration of such regulation that may be the cause of the observed abnormal INCREASE of the intensity of proliferation of some cell populations in old age, resulting in senile acromegaly and age-related rise of numerous benign tumors. It seems that the quality of the cells themselves does not worsen with age as much as reliability of the organism CONTROL over cells, organs and tissues, which leads to an increase in the probability of death.
authors.forename: A N
authors.initials: AN
authors.lastname: Khokhlov
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D016922:Cellular Senescence; D006801:Humans; D008954:Models, Biological; D012038:Regeneration