Cellular Senescence of Lens Epithelial Cells and Age-Related Cataract: A Systematic Review

Recent evidence links lens epithelial cell (LEC) dysfunction and cellular senescence-an irreversible cell cycle arrest with a pro-inflammatory secretory phenotype-to age-related cataract (ARC) progression. This systematic review synthesizes current knowledge on LEC senescence, its molecular features, and laboratory methods for senescence assessment in the ARC. Following PRISMA guidelines, a comprehensive search of PubMed, Scopus and Cochrane databases retrieved 3417 records from inception to 9 February 2025, with 14 studies ultimately included (821 patients and multiple in vitro LEC models). The following multiple senescence expression pathways were identified: SA-β-gal activity, p53/p21 and p16INK4A pathway activation, mitochondrial dysfunction, oxidative stress, and secretion of senescence-associated secretory phenotype (SASP) factors. Notably, cortical cataract demonstrated direct association with local senescent cell accumulation, while nuclear cataract reflected cumulative oxidative damage from impaired LEC-mediated antioxidant defense. Senescence markers correlated positively with cataract severity across multiple studies. Several potential therapeutic targets emerged, including metformin (AMPK activation/autophagic restoration), circMRE11A silencing, NLRP3 inflammasome inhibition, and modulation of FYCO1/PAK1 and MMP2 pathways. This review establishes LEC senescence as a central process in ARC pathogenesis and highlights promising senotherapeutic approaches. Future research should prioritize human surgical samples, develop standardized senescence detection panels (SA-β-gal + p21/p16 + SASP factors), and conduct longitudinal studies to establish causal relationships between senescence accumulation and cataract progression.