General hallmarks of cellular senescence. Markers strongly associated with senescence and seen in the majority of senescent cells include an enlarged size and flattened shape. The other features shown in this figure are not exclusive to senescence but are collectively considered hallmarks of the phenomenon. Senescent cells commonly exhibit the activation of the p53 and/or p16 pathways leading to irreversible cell cycle arrest, chromatin changes, and nuclear envelope disturbance. An increased lysosomal mass leading to enhanced SA-β-galactosidase activity is also often seen and, thus, SA-β-galactosidase activity is probably the most frequently used marker of senescence. Senescent cells may also exhibit strong paracrine secretion (SASP), severe mitochondrial disturbance associated with the activation of anti-apoptotic pathways, and other various characteristics.