Cellular Senescence and Aging: Mechanisms, Disease Convergence, and Therapeutic Frontiers

Abstract

Cellular senescence, a stress-induced, irreversible cell cycle arrest coupled with a proinflammatory secretory phenotype, has emerged as both a central driver of aging and a tractable therapeutic target. Although acute senescence contributes beneficially to tumor suppression and wound healing, chronic accumulation of senescent cells sustains systemic inflammaging and accelerates organ dysfunction. This review synthesizes current progress in aging biology into a unified mechanistic and translational framework. We first examine how primary aging hallmarks, such as genomic instability and epigenetic dysregulation, interact to trigger cellular senescence, then explore how these converging molecular processes give rise to distinct age-related pathologies across reproductive, pulmonary, hepatic, neurological, skeletal, and metabolic systems. We further evaluate emerging interventional strategies, from senolytics and senomorphics to rejuvenation approaches, while addressing key translational barriers including targeting specificity, senescence heterogeneity, and equitable access. By uniting mechanistic insight with disease-oriented and therapeutic perspectives, this review charts a strategic roadmap for deploying senescence-targeting therapies to extend human healthspan.

Keywords

aging hallmarks / age-associated diseases / aging mechanisms / antiaging strategies / cellular senescence

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