Fig. 1.

Central regulators of cellular senescence. p16 and p21 are upregulated upon DNA damage and are the most important CDKIs that contribute to senescence‐associated cell cycle arrest. p53 is the major transcription factor that mediates DNA damage‐induced p21 activation. These CDKIs suppress de‐repression of E2F transcription factors that is mediated by CDK‐dependent phosphorylation of E2F repressor Rb. Cyclin D1 is known to be upregulated in senescent cells but it is reported to be dysfunctional [160]. [Colour figure can be viewed at wileyonlinelibrary.com]