The multifaceted inducers of cellular senescence

Cellular senescence is a stable form of cell-cycle arrest induced by diverse intrinsic and extrinsic stimuli. While senescence contributes to tumor suppression, wound repair, and placental and embryonic development, the chronic accumulation of senescent cells promotes tissue dysfunction, chronic inflammation, tumorigenesis, and age-related diseases. This review provides a comprehensive overview of the major inducers of cellular senescence, including DNA damage, oxidative and mitochondrial stress, telomere attrition, oncogene activation, cell–cell fusion, senescence-induced senescence and developmental stimuli, and summarizes the molecular mechanisms through which they trigger the senescence program. Although these stimuli differ widely, many converge to core effector pathways, resulting in a stable growth arrest. Understanding the varied stimuli and their underlying mechanisms of senescence induction is crucial for revealing the heterogeneity of senescent cells and developing interventions that modulate senescence during aging and disease.