Senescent

Senescent is a term used in biology to describe cells or tissues that have ceased to divide permanently, usually in response to stress, damage, or aging. A senescent cell remains metabolically active but enters a stable cell-cycle arrest, distinguishing it from quiescent cells that can re-enter the cell cycle.

Cellular senescence is a tumor-suppressive mechanism and a contributor to aging. Triggers include telomere shortening after repeated divisions (replicative senescence), DNA damage, oxidative stress, radiation, chemotherapy, and oncogene activation. Key signaling pathways involve p53/p21 and p16INK4a/pRB. Senescent cells often develop a characteristic secretory profile known as the senescence-associated secretory phenotype (SASP), which includes inflammatory cytokines, chemokines, proteases, and growth factors.

Physiological roles of senescence include embryonic development, tissue remodeling, and wound healing, where it helps to limit proliferation and promote regeneration. However, accumulation of senescent cells with age contributes to chronic inflammation and tissue dysfunction, partly through SASP factors, and is linked to several age-related diseases.

Detection and markers of senescence are not universal; researchers look for increased p16INK4a or p21 expression, senescence-associated beta-galactosidase activity, and DNA damage indicators such as γ-H2AX. A combination of markers is typically used.

Clinical relevance and research: Senescence is a focus of aging and cancer research. Therapies that aim to remove senescent cells (senolytics) or modulate SASP are under investigation, with potential to mitigate age-related pathology but with ongoing questions about safety and efficacy.