Cellular senescence

Cellular senescence is a stable form of cell cycle arrest in which previously proliferating cells lose the capacity to divide in response to various internal or external stressors, including DNA damage, oncogene activation, and telomere shortening. While senescent cells remain metabolically active, they acquire distinct phenotypes, including changes in gene expression, chromatin structure, metabolic activity, and a pro-inflammatory senescence-associated secretory phenotype (SASP)[1][3][6][7]. Senescence prevents the propagation of damaged cells, thus acting as a tumor-suppressive mechanism, but accumulation of senescent cells contributes to aging and a variety of age-related diseases, including cancer, fibrosis, and neurodegeneration. Because senescence itself is not a discrete molecule, receptor, or typical therapeutic target, but rather a stress response program involving multiple molecular pathways (notably the p53/p21 and p16^INK4a^/RB pathways), efforts to therapeutically modulate senescence focus on targeting senescent cells for removal (senolytics) or for modulation of their harmful secretion (senomorphics)[2][8].

Other names

SenescenceCellular agingReplicative senescenceStress-induced senescence

Senolytic (elimination of senescent cells via targeting anti-apoptotic pathways such as BCL-2 family) Senomorphic (suppression of SASP or senescence-associated secretory phenotype, e.g., via mTOR or NF-κB inhibition)[2][8]