Recently, a large number of papers have appeared that describe the successful use of various biologically active compounds (short peptides, mitochondrial antioxidants, antidiabetic biguanides,...

We believe that cytogerontological models, such as the Hayflick model, though very useful for experimental gerontology, are based only on certain correlations and do not directly apply to the gist of the aging process. Thus, the Hayflick limit concept cannot explain why we age, whereas our “stationary phase aging” model appears to be a “gist model,” since it is based on the hypothesis that the main cause of both various “age-related” changes in stationary cell cultures and similar changes in the cells of aging multicellular organism is the restriction of cell proliferation. The model is applicable to experiments on a wide variety of cultured cells, including normal and transformed animal and human cells, plant cells, bacteria, yeasts, mycoplasmas, etc. The results of relevant studies show that cells in this model die out in accordance with the Gompertz law, which describes exponential increase of the death probability with time. Therefore, the “stationary phase aging” model may prove effective in testing of various geroprotectors (anti-aging factors) and geropromoters (pro-aging factors) in cytogerontological experiments. It should be emphasized, however, that even the results of such experiments do not always agree with the data obtained in vivo and therefore cannot be regarded as final but should be verified in studies on laboratory animals and in clinical trials (provided this complies with ethical principles of human subject research).

There is an opinion that the chronological aging (ChA) of yeast and the stationary phase aging (SPA) of cultured animal and human cells are a consequence of growth medium acidification. However, a number of recent publications indicate that, although this process has a certain influence on the rate of “aging” of cells in the stationary growth phase, it does not determine it completely. Apparently, the key factor in this case is the restriction of cell proliferation, which leads to cell “aging” even under physiologically optimal conditions. During yeast ChA and mammalian cell SPA, the medium is getting acidified to pH ≤ 4. Prevention of acidification can prolong the culture life span, but the cells will still die, although at a slower rate. Effects of medium acidification during ChA and SPA can be explained by activation of highly conserved growth signaling pathways leading to oxidative stress, and these processes, in turn, can play a role in aging of multicellular organisms and development of age-related diseases. Our previous experiments on the effect of buffer capacity of growth medium on SPA of transformed Chinese hamster cells showed that 20 mM HEPES had no effect on cell growth rate; in addition, the growth curves of experimental and control cells reached a plateau on the same day. However, the cell saturation density in the medium with HEPES was lower (i.e., the cells were “older” in terms of the gerontological cell kinetics model); on the other hand, the rate of SPA was markedly reduced, compared to the control, although the cells were still “getting older.” It can be assumed that extracellular pH (by the way, well correlated with intracellular pH) is an important factor (I.A. Arshavsky’s concept of the role of acidic alteration in aging) but not the key factor determining the survival of cells in a stationary culture.

Aging organisms die out in accordance with the “Gompertz law,” i.e., the probability of their death increases with age. Survival curve construc

Despite the great interest of scientists in the question of what cell aging is and the long history of its study, there are still many contradictions in th