Senescence-associated β-galactosidase—A biomarker of aging, DNA damage, or cell proliferation restriction?

The most popular biomarker of cellular senescence (BCS) is the activity of senescence-associated β-galactosidase (SA-β-Gal). Today, this is the prevailing BCS in the studies based on the definition of cell senescence (which we do not accept) understood primarily as accumulation in the cells (most often—those not prone to replicative senescence) of certain BCS under the impact of various external factors causing DNA damage. However, some papers provide evidence that SA-β-Gal activity in the cells is not a good BCS, because it often depends not so much on age (in vitro or in vivo) as on the method of research, the presence of certain pathologies, and, what is most important, on the proliferative status of the cells studied. Apparently, the restriction of cell proliferation under certain conditions (due to differentiation, contact inhibition, DNA damage, some diseases, etc.) is itself the factor that stimulates SA-β-Gal expression. In other words, SA-β-Gal appears even in “young” cells if their proliferation is suppressed. Such data, in our opinion, are additional evidence for the validity of our concept of aging, which postulates the leading role of cell proliferation restriction in the age-related accumulation of various macromolecular defects (primarily DNA damage) in cells.