Senotherapeutics: emerging pharmacological strategies for targeting cellular senescence

Cellular senescence(definition) is a complex biological state characterized by persistent cell-cycle arrest and profound changes in cellular function. Although senescence contributes to tissue repair, tumor suppression and physiological homeostasis, the persistent accumulation of senescent cells promotes chronic inflammation, tissue dysfunction, aging and several age-associated diseases. Senotherapeutics have therefore emerged as promising pharmacological approaches for selectively targeting senescent cells and limiting their detrimental effects. This review summarizes the biological characteristics of cellular senescence, including major molecular markers and approaches used for its induction and detection. Particular emphasis is placed on senolytics(definition), which selectively eliminate senescent cells by targeting their pro-survival mechanisms and senomorphics, which suppress harmful senescent-cell functions, particularly senescence-associated secretory phenotype (SASP) signaling. Established and emerging senolytic agents, including BCL-2 family inhibitors, dasatinib, quercetin, fisetin and novel small molecules, are discussed. Recent advances in artificial intelligence-assisted drug discovery, phenotypic screening and computational modeling are highlighted as emerging tools for identifying new senotherapeutic candidates. Gene-based approaches involving genome editing, RNA modulation, epigenetic regulation and targeted delivery systems are also considered for precise modulation of cellular senescence. Despite promising advances, cellular heterogeneity, limited target specificity, off-target effects, tissue delivery and long-term safety remain major challenges for clinical translation. Integrating molecular biomarkers, multi-omics technologies, computational approaches and pharmacological strategies may facilitate the development of safer and more selective senotherapeutics. Overall, senotherapeutics represent an evolving therapeutic field with considerable potential for targeting cellular senescence, mitigating age-associated pathology and ultimately supporting healthy aging and extending healthspan(definition).