Cellular senescence is a response to nonlethal stress that results in a persistent and often extremely stable cell cycle arrest. Among the most prominent intrinsic stimuli that induce a senescence response are genomic and epigenomic perturbations many of which can initiate or promote aging and age-related diseases. The underlying mechanisms for these perturbations are largely unknown. Senescence-inducing stimuli include progressive telomere shortening (replicative senescence) but also other stimuli that by-and-large do not impact telomere integrity such as oncogenic signaling (oncogene-induced senescence), DNA damage, oxidative stress and cytokines among others.