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Evolution of the term “cellular senescence” and its impact on the current cytogerontological research

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Abstract

The term “cellular/cell senescence” was first introduced by Leonard Hayflick to describe the “age-related” changes in normal eukaryotic cells during aging in vitro, i.e., over the exhaustion of their mitotic potential. In the “classic” variant, it was assumed that cells “grow old” with the help of some internal mechanism, which leads to accumulation of various macromolecular defects (DNA damage in the first place). Currently, as a rule, “cellular senescence” means accumulation/appearance of particular “biomarkers of aging” in cells (they are most often transformed cells that do not demonstrate any replicative senescence) 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 the said biomarkers, there are senescence-associated beta-galactosidase activity, expression of p53 and p21 proteins as well as of proteins involved in the regulation of inflammation, such as IL-6 or IL-8, activation of oncogenes, etc. Thus, “aging/senescence” of cells does not occur simply by itself—it takes place because of the influence of DNA-damaging agents. This approach, in my opinion, despite being very important to define a strategy to fight cancer, distracts us, yet again, from the study of the real mechanisms of aging. It should be emphasized that the “stationary phase aging” model developed in my laboratory also allows registering 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, i.e., due to a rather physiological impact, which does not cause any damage to cells by itself (the situation is similar to what we observe in a whole multicellular organism).

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  1. Evolutionary Cytogerontology Sector, Biological Faculty, Moscow State University, Moscow, Russia

    A. N. Khokhlov

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Correspondence to A. N. Khokhlov.

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Original Russian Text © A.N. Khokhlov, 2013, published in Vestnik Moskovskogo Universiteta. Biologiya, 2013, No. 4, pp. 18–22.

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Khokhlov, A.N. Evolution of the term “cellular senescence” and its impact on the current cytogerontological research. Moscow Univ. Biol.Sci. Bull. 68, 158–161 (2013). https://doi.org/10.3103/S0096392513040123

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