Senescent cell heterogeneity: origins, detection, and therapeutic implications

Although senescent cells are commonly characterized by stable cell cycle arrest, emerging evidence indicates that senescence is not a uniform state but a collection of highly heterogeneous phenotypes. This heterogeneity stems from biological factors, such as diverse senescence markers, cellular origins, and targeting mechanisms, as well as from technical variations in experimental approaches, notably in the design of transgenic mouse models. By summarizing recent advances in next-generation senolytic strategies, multiomics profiling, and genetically engineered mouse models of senescence, we provide an integrated perspective on the origins and consequences of senescent cell heterogeneity. Such a perspective is essential for refining investigative methodologies and for developing precise therapies that selectively target senescent cell populations whose roles have been experimentally validated in vivo.