CELLULAR SENESCENCE: MOLECULAR MECHANISMS AND SENOLYTIC AND SENOMORPHIC STRATEGIES

Abstract

Cellular senescence is an irreversible cell cycle arrest associated with chronic inflammation and age-related diseases. Senescent cells develop a senescence-associated secretory phenotype (SASP), largely regulated by NF-κB signaling, which promotes tissue dysfunction and inflammaging. Key molecular pathways involved in senescence include p53/p21, p16INK4a/Rb, and SIRT1-mediated regulation. Recent therapeutic strategies focus on senolytics, which selectively eliminate senescent cells, and senomorphics, which suppress their harmful phenotype without inducing cell death. Natural flavonoids such as quercetin and rutin have shown promising senomorphic and context-dependent senolytic effects through antioxidant activity, NF-κB inhibition, and SIRT1 activation. This review summarizes the molecular mechanisms of cellular senescence and highlights current senotherapeutic approaches with emphasis on SIRT1 and flavonoid-based interventions as potential anti-aging strategies.