EVOLUTION OF THE TERM “CELLULAR SENESCENCE” AND IMPACT OF THIS EVOLUTION ON THE CURRENT CYTOGERONTOLOGICAL RESEARCH

The term “cellular senescence” (“cell senescence”) was put into circulation by Leonard Hayflick to describe the “age-related” changes in normal eukaryotic cells during aging in vitro, i.e., the exhaustion of their mitotic potential. In the “classic” version it was implied that the cells “grow old” with the help of some internal mechanism that leads to accumulation of various intracellular macromolecular defects (primarily — DNA damage). At present, as a rule, speaking of “cellular senescence” means accumulation/appearance in the cells (most often — transformed cells which do not demonstrate replicative senescence) of certain “biomarkers of aging” under the influence of various external
factors (oxidative stress, H2O2, mitomycin C, ethanol, ionizing radiation, doxorubicin, etc.) that cause DNA damage. This phenomenon has been called DDR (DNA Damage Response). Among these biomarkers — senescence-associated beta-galactosidase activity, expression of p53 and p21 proteins, as well as of proteins involved in the regulation of inflammation like IL-6 or IL-8, activation of oncogenes, etc. Thus, “aging/senescence” of the cells does not occur by itself, but because of the impact of DNA-damaging agents. This approach, in my opinion, although is very important to define a strategy to fight cancer, but, yet again, takes us away from the study of the real mechanisms of aging. It should be emphasized that within the scope of “stationary phase aging” model developed in my lab, we also register the occurrence of certain biomarkers of aging in cultured cells, but in this case they arise due to the restriction of their proliferation by contact inhibition — a rather physiological impact, which in itself does not cause any damage to the cells (the situation is very similar to what we see in a whole multicellular organism).

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