{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T08:11:29Z","timestamp":1780647089453,"version":"3.54.1"},"reference-count":39,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Recent evidence links lens epithelial cell (LEC) dysfunction and cellular senescence\u2014an irreversible cell cycle arrest with a pro-inflammatory secretory phenotype\u2014to 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-\u03b2-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-\u03b2-gal + p21\/p16 + SASP factors), and conduct longitudinal studies to establish causal relationships between senescence accumulation and cataract progression.<\/jats:p>","DOI":"10.3390\/bioengineering13040433","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T07:25:12Z","timestamp":1775633112000},"page":"433","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cellular Senescence of Lens Epithelial Cells and Age-Related Cataract: A Systematic Review"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-3697-8713","authenticated-orcid":false,"given":"Anastasia","family":"Kourtesa","sequence":"first","affiliation":[{"name":"2nd Department of Pathology, University General Hospital \u201cAttikon\u201d, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0994-4959","authenticated-orcid":false,"given":"Konstantinos","family":"Skarentzos","sequence":"additional","affiliation":[{"name":"2nd Department of Pathology, University General Hospital \u201cAttikon\u201d, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1583-0931","authenticated-orcid":false,"given":"Georgios S.","family":"Dimtsas","sequence":"additional","affiliation":[{"name":"1st Department of Ophthalmology, General Hospital of Athens \u201cG. Gennimatas\u201d, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6053-7841","authenticated-orcid":false,"given":"Periklis G.","family":"Foukas","sequence":"additional","affiliation":[{"name":"2nd Department of Pathology, University General Hospital \u201cAttikon\u201d, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilita","family":"Moschos","sequence":"additional","affiliation":[{"name":"1st Department of Ophthalmology, General Hospital of Athens \u201cG. Gennimatas\u201d, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1097\/ICU.0000000000000340","article-title":"The global state of cataract blindness","volume":"28","author":"Lee","year":"2017","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1038\/s41433-020-0806-3","article-title":"Global and regional prevalence of age-related cataract: A comprehensive systematic review and meta-analysis","volume":"34","author":"Hashemi","year":"2020","journal-title":"Eye"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1055\/a-2003-2369","article-title":"Cataract Classification Systems: A Review","volume":"241","author":"Mackenbrock","year":"2024","journal-title":"Klin. Monbl. 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