Figure 1.

An overview of the morphological, cellular, and epigenomic changes that occur as cell senescence. Morphological alterations include cellular flattening and enlargement. Cellular lysosomal content increases concomitantly with the elevated expression of senescence-associated β-galactosidase, a highly specific marker for senescence [19]. Mitochondrial abnormalities include impaired biogenesis and mitophagy along with increased reactive oxygen species production and decreased membrane potential [20]. Senescent cells also secrete a heterogeneous group of proinflammatory cytokines, chemokines, proteases, and growth factors that have a profound impact on neighboring cells, known as senescence-associated secretory phenotype (SASP). Large-scale chromatin reorganization occurs with the generation of senescence-associated heterochromatin foci (SAHF), which specifically suppress transcription of pro-proliferation genes [23]. Global hypomethylation of DNA is observed in replicative senescence [29]. Histone variant deposition, histone tail acetylation/methylation, and DNA methylation encompass many of the epigenomic alterations that initiate and maintain cellular senescence.