Cellular senescence: Role in ageing, diseases and therapeutics: A review

Cellular senescence is a state of stable, irreversible proliferative arrest in which damaged cells exit the cell cycle while retaining metabolic activity and actively resisting apoptosis. Since its initial description by Hayflick and Moorhead in 1961, senescence has emerged as a pivotal biological process with wide-ranging consequences for tissue homeostasis, aging, and disease. Senescent cells are distinguished by persistent cell cycle arrest, nuclear chromatin reorganization, and the senescence-associated secretory phenotype (SASP)-a collection of pro-inflammatory cytokines, proteases, and growth factors that profoundly alters the tissue microenvironment. Their progressive accumulation with age drives chronic low-grade inflammation, disrupts stem cell niches, and impairs organ function. Senescence is initiated by diverse stimuli including telomere attrition, oncogene activation, genotoxic and oxidative stress, and mitochondrial dysfunction, converging on the p53/p21 and p16INK4A/pRB tumor suppressor pathways. Pathologically, senescent cell burden underpins major age-related conditions such as osteoarthritis, idiopathic pulmonary fibrosis, atherosclerosis, and cancer — where it plays a paradoxical dual role as both a tumor suppressor and a promoter of malignancy. Established biomarkers including SA-β-galactosidase activity, p16INK4A expression, phosphorylated p53, and Lamin B1 downregulation enable identification of senescent cells in experimental and clinical contexts. Senotherapy-comprising senolytics that selectively eliminate senescent cells and senomorphics that attenuate SASP offers transformative potential for healthspan extension and disease modification. This review integrates current mechanistic understanding with translational perspectives on cellular senescence in aging and disease.