The role of DNA damage in cellular aging: is it time for a reassessment?
There is now evidence that the immediate cause of the loss of proliferative capacity in senescent cells is mediated by a specific inhibitor. If this tentative interpretation is correct, the next hurdle will be to determine mechanism(s) that regulate this putative senescence cell inhibitor that would, in effect, be the determinant of proliferative life span. One previously proposed hypothesis predicts that the decline of replicative activity is analogous to a checkpoint response to accumulated chromosomal damage (Rosenberger et al., 1991). Advances in our basic understanding of the nature of DNA damage, DNA repair mechanisms, and the response of eukaryotic cells to accumulated DNA damage provide a solid rationale for a reassessment of the causal role of the accumulation of chromosomal damage in cell senescence in vitro.
Norwood
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Department of Pathology, University of Washington, Seattle 98195-7470, USA.
Gray
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D000818:Animals; D016922:Cellular Senescence; D004249:DNA Damage; D004260:DNA Repair; D006801:Humans