Senescence

Senescence is a cellular state characterized by permanent arrest of cell division in response to stress, accompanied by active metabolism and changes in gene expression. It occurs in many cell types and tissues and plays a central role in aging and tissue homeostasis. A key distinction is between replicative senescence, driven by telomere shortening after repeated cell divisions, and stress-induced premature senescence, triggered by DNA damage, oncogene activation, oxidative stress, or other insults.

A hallmark of senescent cells is a stable cell-cycle arrest, often coupled with resistance to apoptosis and the development of a distinctive phenotype. This includes alterations in chromatin structure, metabolic changes, and the upregulation of senescence-associated secretory phenotype (SASP), a complex mix of inflammatory cytokines, chemokines, growth factors, and proteases that can influence neighboring cells and tissue structure.

Biological roles of senescence are diverse. It acts as a tumor-suppressive mechanism by halting the proliferation of damaged cells and contributes to wound healing and embryonic development. Conversely, the accumulation of senescent cells with age and the chronic activity of SASP can promote chronic inflammation, tissue dysfunction, and age-related diseases. The immune system normally helps clear senescent cells, but clearance becomes less efficient with aging.

Biomarkers commonly used to identify senescence include increased p16INK4a expression, p21, and senescence-associated beta-galactosidase activity. Therapeutic approaches are being explored, including senolytics that selectively eliminate senescent cells and SASP modulators that dampen deleterious secretory effects, with ongoing research into their benefits and risks.