Causes Of Cellular Senescence

Cellular senescence was first formally described as the process that limits the proliferation of human cells in culture (12,13). This process—referred to here as replicative senescence—is now known to be driven by the progressive shortening of telomeres (14-18). In recent years, it has become clear that cells arrest growth with a senescent phenotype in response to a variety of stimuli, most, if not all, of which have the potential to cause preneoplastic or neoplastic transformation (see Fig. 1). These stimuli include dysfunctional telomeres, DNA damage, disrupted chromatin structures, the expression of certain oncogenes, and supraphysiological mitogenic signals (19-26). Several lines of evidence strongly support the idea that, at least in mammals, cellular senescence constitutes a fail-safe mechanism to prevent the growth of cells at risk for neoplastic transformation (1,8,10,11,27-29).

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