Cellular Senescence in Health, Disease, and Lens Aging

Background: Cellular senescence(definition) is a state of irreversible cell cycle arrest that serves as a critical regulator of tissue homeostasis, aging, and disease. While transient senes-cence contributes to development, wound healing, and tumor suppression, chronic senescence drives inflammation, tissue dysfunction, and age-related pathologies, in-cluding cataracts. Lens epithelial cells (LECs), essential for maintaining lens transpar-ency, are particularly vulnerable to oxidative stress-induced senescence, which accel-erates lens aging and cataract formation. This review examines the dual role of senes-cence in LEC function and its implications for age-related cataractogenesis, alongside emerging senotherapeutic interventions. Methods: This review synthesizes findings on the molecular mechanisms of senescence, focusing on oxidative stress, mitochon-drial dysfunction, and the senescence-associated secretory phenotype (SASP). It ex-plores evidence linking LEC senescence to cataract formation, highlighting key studies on stress responses, DNA damage, and antioxidant defense. Recent advances in seno-therapeutics, including senolytics(definition) and senomorphics, are analyzed for their potential to mitigate LEC senescence and delay cataract progression. Conclusions: LEC senescence is driven by oxidative damage, mitochondrial dysfunction(definition), and impaired redox home-ostasis. These factors activate senescence path-ways, including p53/p21 and p16/Rb, resulting in cell cycle arrest and SASP-mediated inflammation. The accumulation of senescent LECs re-duces regenerative capacity, disrupts lens homeostasis, and con-tributes to cataractogenesis. Emerging senotherapeutics, such as dasatinib, quercetin, and metformin, show promise in reducing senescent cell burden and modulating SASP to preserve lens transparency.