Senotherapeutics: Emerging pharmacological strategies to target cellular senescence

Abstract Cellular senescence is a fundamental hallmark of aging characterized by irreversible cell cycle arrest, resistance to apoptosis, and the acquisition of a pro-inflammatory senescence-associated secretory phenotype (SASP). While senescence plays beneficial roles in tumor suppression and tissue repair, its accumulation with age contributes to chronic inflammation, tissue dysfunction, and the pathogenesis of multiple age-related diseases. Over the past decade, pharmacological strategies targeting senescent cells—collectively termed senotherapeutics —have emerged as a promising avenue to extend healthspan and mitigate age-related pathology. These approaches include senolytics, which selectively eliminate senescent cells; senomorphics, which suppress the deleterious SASP without inducing cell death; and emerging strategies aimed at modulating immune-mediated clearance and senescence-associated metabolic vulnerabilities. This review provides a comprehensive overview of the molecular mechanisms underpinning cellular senescence, critically evaluates current classes of senotherapeutics, and highlights translational challenges and opportunities for clinical development.