Fig. 3.
Three general phases of cellular senescence. Senescence can be initiated by various factors that lead to the activation of the p53/p21 and p16INK4a/Rb pathways, resulting in an irreversible cell cycle arrest. Early stages of senescence are associated with chromatin remodeling, forming DNA segments with chromatin alterations reinforcing senescence (DNA-SCARS) and telomere-induced dysfunctional foci (TIF) as well as senescence-associated heterochromatin foci (SAHF). Senescent cells start to release various molecules, including chemokines, cytokines, growth factors and others, determining senescence-associated secretory phenotype (SASP). Senescent cells increase mitochondrial metabolism and become resistant to apoptosis. Further changes associated with aging and long-lasting cellular damage result in variation in senescent phenotype and chronic inflammation