Senescent cells as a target for anti-aging interventions: From senolytics to immune therapies.

Aging and age-related diseases are major drivers of multimorbidity and mortality worldwide. Cellular senescence is a hallmark of aging. The accumulation of senescent cells is causally associated with pathogenesis of various age-associated disorders. Due to their promise for alleviating age-related disorders and extending healthspan, therapeutic strategies targeting senescent cells (senotherapies) as a means to combat aging have received much attention over the past decade. Among the conventionally used approaches, one is the usage of small-molecule compounds to specifically exhibit cytotoxicity toward senescent cells or inhibit deleterious effects of the senescence-associated secretory phenotype (SASP). Alternatively, there are immunotherapies directed at surface antigens specifically upregulated in senescent cells (seno-antigens), including chimeric antigen receptor (CAR) therapies and senolytic vaccines. This review gives an update of the current status in the discovery and development of senolytic therapies, and their translational progress from preclinical to clinical trials. We highlight the current challenges faced by senotherapeutic development in the context of senescence heterogeneity, with the aim of offering novel perspectives for future anti-aging interventions aimed at enhancing healthy longevity.