{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:10:13Z","timestamp":1791389413011,"version":"4.3.3"},"reference-count":149,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T00:00:00Z","timestamp":1739318400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health (NIH)","award":["NEI R21EY033941"],"award-info":[{"award-number":["NEI R21EY033941"]}]},{"name":"National Institutes of Health (NIH)","award":["NEI R01EY034529"],"award-info":[{"award-number":["NEI R01EY034529"]}]},{"name":"National Institutes of Health (NIH)","award":["NIH R15GM123463-02"],"award-info":[{"award-number":["NIH R15GM123463-02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Cellular senescence is a state of irreversible cell cycle arrest that serves as a critical regulator of tissue homeostasis, aging, and disease. While transient senescence contributes to development, wound healing, and tumor suppression, chronic senescence drives inflammation, tissue dysfunction, and age-related pathologies, including cataracts. Lens epithelial cells (LECs), essential for maintaining lens transparency, are particularly vulnerable to oxidative stress-induced senescence, which accelerates lens aging and cataract formation. This review examines the dual role of senescence 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, mitochondrial dysfunction, and the senescence-associated secretory phenotype (SASP). It explores evidence linking LEC senescence to cataract formation, highlighting key studies on stress responses, DNA damage, and antioxidant defense. Recent advances in senotherapeutics, including senolytics 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, and impaired redox homeostasis. 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 reduces regenerative capacity, disrupts lens homeostasis, and contributes to cataractogenesis. Emerging senotherapeutics, such as dasatinib, quercetin, and metformin, show promise in reducing the senescent cell burden and modulating the SASP to preserve lens transparency.<\/jats:p>","DOI":"10.3390\/ph18020244","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T03:41:57Z","timestamp":1739331717000},"page":"244","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Cellular Senescence in Health, Disease, and Lens Aging"],"prefix":"10.3390","volume":"18","author":[{"given":"Ying","family":"Qin","sequence":"first","affiliation":[{"name":"Pharmaceutical Sciences, College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX 76107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5313-3143","authenticated-orcid":false,"given":"Haoxin","family":"Liu","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences, College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX 76107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongli","family":"Wu","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences, College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX 76107, USA"},{"name":"North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TX 76107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/s41580-020-00314-w","article-title":"Cellular senescence in ageing: From mechanisms to therapeutic opportunities","volume":"22","author":"Krizhanovsky","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.cyto.2019.01.013","article-title":"The senescence-associated secretory phenotype and its regulation","volume":"117","author":"Rowell","year":"2019","journal-title":"Cytokine"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1146\/annurev-pathol-121808-102144","article-title":"The senescence-associated secretory phenotype: The dark side of tumor suppression","volume":"5","author":"Coppe","year":"2010","journal-title":"Annu. Rev. Pathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1089\/ars.2020.8043","article-title":"Cell Senescence, DNA Damage, and Metabolism","volume":"34","author":"Shmulevich","year":"2021","journal-title":"Antioxid. Redox Signal"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1083\/jcb.201708092","article-title":"Senescence and aging: Causes, consequences, and therapeutic avenues","volume":"217","author":"McHugh","year":"2018","journal-title":"J. Cell Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1146\/annurev-physiol-030212-183653","article-title":"Aging, cellular senescence, and cancer","volume":"75","author":"Campisi","year":"2013","journal-title":"Annu. Rev. Physiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1038\/nrm3823","article-title":"Cellular senescence: From physiology to pathology","volume":"15","author":"Serrano","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s41232-024-00342-5","article-title":"Role of cellular senescence in inflammation and regeneration","volume":"44","author":"Saito","year":"2024","journal-title":"Inflamm. Regen."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1038\/s41569-021-00624-2","article-title":"The role of cellular senescence in cardiac disease: Basic biology and clinical relevance","volume":"19","author":"Mehdizadeh","year":"2022","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Katsuumi, G., Shimizu, I., Yoshida, Y., and Minamino, T. (2018). Vascular Senescence in Cardiovascular and Metabolic Diseases. Front. Cardiovasc. Med., 5.","DOI":"10.3389\/fcvm.2018.00018"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1038\/s41571-022-00668-4","article-title":"Senescence and cancer\u2014role and therapeutic opportunities","volume":"19","author":"Schmitt","year":"2022","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1038\/s41568-022-00450-9","article-title":"Exploiting senescence for the treatment of cancer","volume":"22","author":"Wang","year":"2022","journal-title":"Nat. Rev. Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Wyld, L., Bellantuono, I., Tchkonia, T., Morgan, J., Turner, O., Foss, F., George, J., Danson, S., and Kirkland, J.L. (2020). Senescence and Cancer: A Review of Clinical Implications of Senescence and Senotherapies. Cancers, 12.","DOI":"10.3390\/cancers12082134"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"441","DOI":"10.4093\/dmj.2022.0416","article-title":"Regulation of Cellular Senescence in Type 2 Diabetes Mellitus: From Mechanisms to Clinical Applications","volume":"47","author":"Iwasaki","year":"2023","journal-title":"Diabetes Metab. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"869414","DOI":"10.3389\/fendo.2022.869414","article-title":"Cellular Senescence in Diabetes Mellitus: Distinct Senotherapeutic Strategies for Adipose Tissue and Pancreatic \u03b2 Cells","volume":"13","author":"Murakami","year":"2022","journal-title":"Front. Endocrinol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"bqab136","DOI":"10.1210\/endocr\/bqab136","article-title":"Role of Cellular Senescence in Type II Diabetes","volume":"162","author":"Narasimhan","year":"2021","journal-title":"Endocrinology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2289","DOI":"10.2337\/db14-1820","article-title":"Cellular Senescence in Type 2 Diabetes: A Therapeutic Opportunity","volume":"64","author":"Palmer","year":"2015","journal-title":"Diabetes"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Lee, H.J., Yoon, Y.S., and Lee, S.J. (2023). Molecular Mechanisms of Cellular Senescence in Neurodegenerative Diseases. J. Mol. Biol., 435.","DOI":"10.1016\/j.jmb.2023.168114"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"111675","DOI":"10.1016\/j.mad.2022.111675","article-title":"Cellular senescence in the aging brain: A promising target for neurodegenerative diseases","volume":"204","author":"Sahu","year":"2022","journal-title":"Mech. Ageing Dev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2393","DOI":"10.1007\/s00204-024-03768-5","article-title":"The role of cellular senescence in neurodegenerative diseases","volume":"98","author":"Wang","year":"2024","journal-title":"Arch. Toxicol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3067","DOI":"10.1007\/s00417-023-06070-9","article-title":"Cellular senescence and ophthalmic diseases: Narrative review","volume":"261","author":"Soleimani","year":"2023","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2583601","DOI":"10.1155\/2020\/2583601","article-title":"The Emerging Role of Senescence in Ocular Disease","volume":"2020","author":"Sreekumar","year":"2020","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1001\/archophthalmol.2010.147","article-title":"Smoking, socioeconomic factors, and age-related cataract: The Singapore Malay Eye study","volume":"128","author":"Wu","year":"2010","journal-title":"Arch. Ophthalmol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/0014-4827(61)90192-6","article-title":"The serial cultivation of human diploid cell strains","volume":"25","author":"Hayflick","year":"1961","journal-title":"Exp. Cell Res."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Liao, Z., Yeo, H.L., Wong, S.W., and Zhao, Y. (2021). Cellular Senescence: Mechanisms and Therapeutic Potential. Biomedicines, 9.","DOI":"10.3390\/biomedicines9121769"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Rodriguez-Brenes, I.A., Wodarz, D., and Komarova, N.L. (2015). Quantifying replicative senescence as a tumor suppressor pathway and a target for cancer therapy. Sci. Rep., 5.","DOI":"10.1038\/srep17660"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/s41576-019-0099-1","article-title":"Telomeres and telomerase: Three decades of progress","volume":"20","author":"Shay","year":"2019","journal-title":"Nat. Rev. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.3892\/mmr.2020.11274","article-title":"Telomerase and telomeres in aging theory and chronographic aging theory (Review)","volume":"22","author":"Razgonova","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/s41556-022-00842-x","article-title":"Telomere dysfunction in ageing and age-related diseases","volume":"24","author":"Rossiello","year":"2022","journal-title":"Nat. Cell Biol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Saretzki, G. (2023). Role of Telomeres and Telomerase in Cancer and Aging. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24129932"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1158\/2159-8290.CD-16-0062","article-title":"Role of Telomeres and Telomerase in Aging and Cancer","volume":"6","author":"Shay","year":"2016","journal-title":"Cancer Discov."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1080\/00313020600580468","article-title":"The role of telomeres and telomerase in the pathology of human cancer and aging","volume":"38","author":"Shin","year":"2006","journal-title":"Pathology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1002\/em.22087","article-title":"Mechanisms of DNA damage, repair, and mutagenesis","volume":"58","author":"Chatterjee","year":"2017","journal-title":"Environ. Mol. Mutagen."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.gde.2014.06.009","article-title":"Irreparable telomeric DNA damage and persistent DDR signalling as a shared causative mechanism of cellular senescence and ageing","volume":"26","author":"Rossiello","year":"2014","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Kumari, R., and Jat, P. (2021). Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.645593"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6741","DOI":"10.1128\/MCB.20.18.6741-6754.2000","article-title":"Uncoupling between phenotypic senescence and cell cycle arrest in aging p21-deficient fibroblasts","volume":"20","author":"Dulic","year":"2000","journal-title":"Mol. Cell. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"8416763","DOI":"10.1155\/2017\/8416763","article-title":"Oxidative Stress: Harms and Benefits for Human Health","volume":"2017","author":"Pizzino","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/s41573-018-0008-x","article-title":"Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases","volume":"18","author":"Cuadrado","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1703810","DOI":"10.1155\/2017\/1703810","article-title":"Involvement of Nrf2 in Ocular Diseases","volume":"2017","author":"Batliwala","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Faraonio, R. (2022). Oxidative Stress and Cell Senescence Process. Antioxidants, 11.","DOI":"10.3390\/antiox11091718"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.redox.2016.12.001","article-title":"Happily (n)ever after: Aging in the context of oxidative stress, proteostasis loss and cellular senescence","volume":"11","author":"Hohn","year":"2017","journal-title":"Redox Biol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Iakovou, E., and Kourti, M. (2022). A Comprehensive Overview of the Complex Role of Oxidative Stress in Aging, The Contributing Environmental Stressors and Emerging Antioxidant Therapeutic Interventions. Front. Aging Neurosci., 14.","DOI":"10.3389\/fnagi.2022.827900"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1007\/s11357-023-00760-2","article-title":"Effect of Nrf2 loss on senescence and cognition of tau-based P301S mice","volume":"45","author":"Riordan","year":"2023","journal-title":"Geroscience"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1852","DOI":"10.1091\/mbc.e12-09-0666","article-title":"Inhibition of nuclear factor-erythroid 2-related factor (Nrf2) by caveolin-1 promotes stress-induced premature senescence","volume":"24","author":"Volonte","year":"2013","journal-title":"Mol. Biol. Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"102558","DOI":"10.1016\/j.arr.2024.102558","article-title":"Oxidative stress and cell senescence as drivers of ageing: Chicken and egg","volume":"102","year":"2024","journal-title":"Ageing Res. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"724","DOI":"10.15252\/embj.201592862","article-title":"Mitochondria are required for pro-ageing features of the senescent phenotype","volume":"35","author":"Marques","year":"2016","journal-title":"EMBO J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e158447","DOI":"10.1172\/JCI158447","article-title":"Mitochondrial dysfunction in cell senescence and aging","volume":"132","author":"Miwa","year":"2022","journal-title":"J. Clin. Investig."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1111\/febs.16361","article-title":"Cellular senescence: All roads lead to mitochondria","volume":"290","author":"Martini","year":"2023","journal-title":"FEBS J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/bjd.12208","article-title":"The role of mitochondrial function and cellular bioenergetics in ageing and disease","volume":"169","author":"Brand","year":"2013","journal-title":"Br. J. Dermatol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0005-2728(00)00234-6","article-title":"How understanding the control of energy metabolism can help investigation of mitochondrial dysfunction, regulation and pharmacology","volume":"1504","author":"Murphy","year":"2001","journal-title":"Biochim. Biophys. Acta (BBA) Bioenerg."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1038\/nrd.2018.174","article-title":"Mitochondria as a therapeutic target for common pathologies","volume":"17","author":"Murphy","year":"2018","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1111\/acel.12060","article-title":"Oxidative stress activates a specific p53 transcriptional response that regulates cellular senescence and aging","volume":"12","author":"Gambino","year":"2013","journal-title":"Aging Cell"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1089\/ars.2010.3644","article-title":"p53, oxidative stress, and aging","volume":"15","author":"Liu","year":"2011","journal-title":"Antioxid. Redox Signal"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1016\/j.tem.2024.02.008","article-title":"Metabolic remodeling in cancer and senescence and its therapeutic implications","volume":"35","author":"Kim","year":"2024","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1038\/s42255-021-00483-8","article-title":"The metabolic roots of senescence: Mechanisms and opportunities for intervention","volume":"3","author":"Wiley","year":"2021","journal-title":"Nat. Metab."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Zhang, H., Zhou, H., Shen, X., Lin, X., Zhang, Y., Sun, Y., Zhou, Y., Zhang, L., and Zhang, D. (2023). The role of cellular senescence in metabolic diseases and the potential for senotherapeutic interventions. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1276707"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5","DOI":"10.5483\/BMBRep.2019.52.1.291","article-title":"Metabolic features and regulation in cell senescence","volume":"52","author":"Kwon","year":"2019","journal-title":"BMB Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/s41580-019-0199-y","article-title":"mTOR at the nexus of nutrition, growth, ageing and disease","volume":"21","author":"Liu","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1038\/s43587-023-00416-y","article-title":"Targeting the biology of aging with mTOR inhibitors","volume":"3","author":"Mannick","year":"2023","journal-title":"Nat. Aging"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e12746","DOI":"10.1111\/acel.12746","article-title":"The effects of graded caloric restriction: XII. Comparison of mouse to human impact on cellular senescence in the colon","volume":"17","author":"Fontana","year":"2018","journal-title":"Aging Cell"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.mad.2018.10.005","article-title":"Caloric restriction and cellular senescence","volume":"176","author":"Fontana","year":"2018","journal-title":"Mech. Ageing Dev."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e14038","DOI":"10.1111\/acel.14038","article-title":"Calorie restriction reduces biomarkers of cellular senescence in humans","volume":"23","author":"Aversa","year":"2024","journal-title":"Aging Cell"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/nrm3270","article-title":"The unfolded protein response: Controlling cell fate decisions under ER stress and beyond","volume":"13","author":"Hetz","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"C415","DOI":"10.1152\/ajpcell.00334.2014","article-title":"The unfolded protein response and cellular senescence. A review in the theme: Cellular mechanisms of endoplasmic reticulum stress signaling in health and disease","volume":"308","author":"Pluquet","year":"2015","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Ziegler, D.V., Martin, N., and Bernard, D. (2021). Cellular senescence links mitochondria-ER contacts and aging. Commun. Biol., 4.","DOI":"10.1038\/s42003-021-02840-5"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Lee, J.H., and Lee, J. (2022). Endoplasmic Reticulum (ER) Stress and Its Role in Pancreatic \u03b2-Cell Dysfunction and Senescence in Type 2 Diabetes. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23094843"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"L126","DOI":"10.1152\/ajplung.00264.2023","article-title":"Endoplasmic reticulum stress-induced senescence in human lung fibroblasts","volume":"327","author":"Drake","year":"2024","journal-title":"Am. J. Physiol.-Lung Cell. Mol. Physiol."},{"key":"ref_68","first-page":"1186","article-title":"The discovery of oncogene-induced senescence","volume":"290","author":"Takahashi","year":"2024","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Toropov, A.L., Deryabin, P.I., Shatrova, A.N., and Borodkina, A.V. (2023). Oncogene-Induced Senescence Is a Crucial Antitumor Defense Mechanism of Human Endometrial Stromal Cells. Int. J. Mol. Sci., 24.","DOI":"10.20944\/preprints202307.1756.v1"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1038\/aps.2017.198","article-title":"Oncogene-induced senescence: A double edged sword in cancer","volume":"39","author":"Liu","year":"2018","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1016\/j.trecan.2020.05.004","article-title":"Senescent Cells in Cancer Therapy: Friends or Foes?","volume":"6","author":"Wang","year":"2020","journal-title":"Trends Cancer"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1111\/febs.15570","article-title":"A guide to assessing cellular senescence in vitro and in vivo","volume":"288","author":"Baker","year":"2021","journal-title":"FEBS J."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"9363","DOI":"10.1073\/pnas.92.20.9363","article-title":"A biomarker that identifies senescent human cells in culture and in aging skin in vivo","volume":"92","author":"Dimri","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Valieva, Y., Ivanova, E., Fayzullin, A., Kurkov, A., and Igrunkova, A. (2022). Senescence-Associated \u03b2-Galactosidase Detection in Pathology. Diagnostics, 12.","DOI":"10.3390\/diagnostics12102309"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1111\/acel.12545","article-title":"Robust, universal biomarker assay to detect senescent cells in biological specimens","volume":"16","author":"Evangelou","year":"2017","journal-title":"Aging Cell"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3","DOI":"10.18632\/aging.100871","article-title":"Markers of cellular senescence. Telomere shortening as a marker of cellular senescence","volume":"8","author":"Bernadotte","year":"2016","journal-title":"Aging"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mrrev.2015.07.001","article-title":"Persistent \u03b3H2AX: A promising molecular marker of DNA damage and aging","volume":"766","author":"Siddiqui","year":"2015","journal-title":"Mutat. Res. Rev. Mutat. Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e13398","DOI":"10.1111\/cpr.13398","article-title":"DNA damage-induced cellular senescence is regulated by 53BP1 accumulation in the nuclear foci and phase separation","volume":"56","author":"Oda","year":"2023","journal-title":"Cell Prolif."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Wang, A.S., and Dreesen, O. (2018). Biomarkers of Cellular Senescence and Skin Aging. Front. Genet., 9.","DOI":"10.3389\/fgene.2018.00247"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1038\/ncomms1708","article-title":"Telomeres are favoured targets of a persistent DNA damage response in ageing and stress-induced senescence","volume":"3","author":"Hewitt","year":"2012","journal-title":"Nat. Commun."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.15252\/embr.201439245","article-title":"Senescence and apoptosis: Dueling or complementary cell fates?","volume":"15","author":"Childs","year":"2014","journal-title":"EMBO Rep."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2629","DOI":"10.1016\/j.jmb.2019.05.036","article-title":"Regulation of Survival Networks in Senescent Cells: From Mechanisms to Interventions","volume":"431","author":"Quax","year":"2019","journal-title":"J. Mol. Biol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"7923","DOI":"10.1038\/s41467-022-35657-9","article-title":"Targeting anti-apoptotic pathways eliminates senescent melanocytes and leads to nevi regression","volume":"13","author":"Kohli","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/bs.pmbts.2015.04.006","article-title":"Overview of the Lens","volume":"134","author":"Hejtmancik","year":"2015","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/0014-4835(77)90143-9","article-title":"Men have heavier lenses than women of the same age","volume":"25","author":"Harding","year":"1977","journal-title":"Exp. Eye Res."},{"key":"ref_86","first-page":"252","article-title":"Growth of the human eye lens","volume":"13","author":"Augusteyn","year":"2007","journal-title":"Mol. Vis."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/j.exer.2010.01.013","article-title":"On the growth and internal structure of the human lens","volume":"90","author":"Augusteyn","year":"2010","journal-title":"Exp. Eye Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/j.preteyeres.2004.06.003","article-title":"Expression, regulation and function of Na,K-ATPase in the lens","volume":"23","author":"Delamere","year":"2004","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1089\/ars.2008.2119","article-title":"Oxidative stress, lens gap junctions, and cataracts","volume":"11","author":"Berthoud","year":"2009","journal-title":"Antioxid. Redox Signal"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/S1350-9462(03)00050-8","article-title":"Redox regulation in the lens","volume":"22","author":"Lou","year":"2003","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Lou, M.F. (2022). Glutathione and Glutaredoxin in Redox Regulation and Cell Signaling of the Lens. Antioxidants, 11.","DOI":"10.3390\/antiox11101973"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1111\/ceo.13892","article-title":"Cataract and systemic disease: A review","volume":"49","author":"Ang","year":"2021","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"15014","DOI":"10.1038\/nrdp.2015.14","article-title":"Cataract","volume":"1","author":"Lam","year":"2015","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_94","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_95","doi-asserted-by":"crossref","unstructured":"Mencucci, R., Stefanini, S., Favuzza, E., Cennamo, M., De Vitto, C., and Mossello, E. (2023). Beyond vision:Cataract and health status in old age, a narrative review. Front. Med., 10.","DOI":"10.3389\/fmed.2023.1110383"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1016\/j.jcrs.2004.02.076","article-title":"Morphology of and visual performance with posterior subcapsular cataract","volume":"30","author":"Vasavada","year":"2004","journal-title":"J. Cataract. Refract. Surg."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/eye.1993.14","article-title":"The morphology of cataract and visual performance","volume":"7","author":"Brown","year":"1993","journal-title":"Eye"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"e000060","DOI":"10.1136\/bmjopen-2011-000060","article-title":"Morphology of traumatic cataract: Does it play a role in final visual outcome?","volume":"1","author":"Shah","year":"2011","journal-title":"BMJ Open"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"e3869","DOI":"10.1097\/MD.0000000000003869","article-title":"Effects of senescent lens epithelial cells on the severity of age-related cortical cataract in humans: A case-control study","volume":"95","author":"Fu","year":"2016","journal-title":"Medicine"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2699","DOI":"10.18632\/aging.101943","article-title":"Laminin \u03b14 overexpression in the anterior lens capsule may contribute to the senescence of human lens epithelial cells in age-related cataract","volume":"11","author":"Yan","year":"2019","journal-title":"Aging"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Zhang, Z.F., Zhang, J., Hui, Y.N., Zheng, M.H., Liu, X.P., Kador, P.F., Wang, Y.S., Yao, L.B., and Zhou, J. (2011). Up-regulation of NDRG2 in senescent lens epithelial cells contributes to age-related cataract in human. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0026102"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.biocel.2007.10.034","article-title":"The lens epithelium: Focus on the expression and function of the \u03b1-crystallin chaperones","volume":"40","author":"Andley","year":"2008","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Parreno, J., Emin, G., Vu, M.P., Clark, J.T., Aryal, S., Patel, S.D., and Cheng, C. (2022). Methodologies to unlock the molecular expression and cellular structure of ocular lens epithelial cells. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.983178"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Wang, Y., Tseng, Y., Chen, K., Wang, X., Mao, Z., and Li, X. (2022). Reduction in Lens Epithelial Cell Senescence Burden through Dasatinib Plus Quercetin or Rapamycin Alleviates D-Galactose-Induced Cataract Progression. J. Funct. Biomater., 14.","DOI":"10.3390\/jfb14010006"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"12955","DOI":"10.1080\/21655979.2022.2079270","article-title":"Senescence marker protein30 protects lens epithelial cells against oxidative damage by restoring mitochondrial function","volume":"13","author":"Teng","year":"2022","journal-title":"Bioengineered"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.freeradbiomed.2016.07.016","article-title":"Mitochondrial oxygen metabolism in primary human lens epithelial cells: Association with age, diabetes and glaucoma","volume":"97","author":"Kubota","year":"2016","journal-title":"Free Radic. Biol. Med."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.1167\/iovs.05-0018","article-title":"Methionine sulfoxide reductases B1, B2, and B3 are present in the human lens and confer oxidative stress resistance to lens cells","volume":"46","author":"Marchetti","year":"2005","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"109521","DOI":"10.1016\/j.exer.2023.109521","article-title":"The impact of glutaredoxin 1 and glutaredoxin 2 double knockout on lens epithelial cell function","volume":"233","author":"Zhang","year":"2023","journal-title":"Exp. Eye Res."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Cvekl, A., and Camerino, M.J. (2022). Generation of Lens Progenitor Cells and Lentoid Bodies from Pluripotent Stem Cells: Novel Tools for Human Lens Development and Ocular Disease Etiology. Cells, 11.","DOI":"10.3390\/cells11213516"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1083\/jcb.130.1.169","article-title":"Lens epithelial cell apoptosis appears to be a common cellular basis for non-congenital cataract development in humans and animals","volume":"130","author":"Li","year":"1995","journal-title":"J. Cell Biol."},{"key":"ref_111","first-page":"2696","article-title":"Human age-related cataract and lens epithelial cell death","volume":"39","author":"Harocopos","year":"1998","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1016\/j.cell.2017.05.015","article-title":"Senescence in Health and Disease","volume":"169","author":"He","year":"2017","journal-title":"Cell"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1101\/gad.343129.120","article-title":"Senescence and the SASP: Many therapeutic avenues","volume":"34","author":"Birch","year":"2020","journal-title":"Genes. Dev."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1111\/febs.16350","article-title":"Targeting cellular senescence with senotherapeutics: Senolytics and senomorphics","volume":"290","author":"Zhang","year":"2023","journal-title":"FEBS J."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1038\/s41591-022-01923-y","article-title":"Cellular senescence and senolytics: The path to the clinic","volume":"28","author":"Chaib","year":"2022","journal-title":"Nat. Med."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1111\/acel.12344","article-title":"The Achilles\u2019 heel of senescent cells: From transcriptome to senolytic drugs","volume":"14","author":"Zhu","year":"2015","journal-title":"Aging Cell"},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Elsallabi, O., Patruno, A., Pesce, M., Cataldi, A., Carradori, S., and Gallorini, M. (2022). Fisetin as a Senotherapeutic Agent: Biopharmaceutical Properties and Crosstalk between Cell Senescence and Neuroprotection. Molecules, 27.","DOI":"10.3390\/molecules27030738"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"111995","DOI":"10.1016\/j.mad.2024.111995","article-title":"Fisetin as a senotherapeutic agent: Evidence and perspectives for age-related diseases","volume":"222","author":"Tavenier","year":"2024","journal-title":"Mech. Ageing Dev."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.ebiom.2018.09.015","article-title":"Fisetin is a senotherapeutic that extends health and lifespan","volume":"36","author":"Yousefzadeh","year":"2018","journal-title":"eBioMedicine"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1111\/acel.12445","article-title":"Identification of a novel senolytic agent, navitoclax, targeting the Bcl-2 family of anti-apoptotic factors","volume":"15","author":"Zhu","year":"2016","journal-title":"Aging Cell"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.cell.2017.02.031","article-title":"Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging","volume":"169","author":"Baar","year":"2017","journal-title":"Cell"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.18632\/aging.102682","article-title":"FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice","volume":"12","author":"Zhang","year":"2020","journal-title":"Aging"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"112522","DOI":"10.1016\/j.exger.2024.112522","article-title":"FOXO4-DRI improves spermatogenesis in aged mice through reducing senescence-associated secretory phenotype secretion from Leydig cells","volume":"195","author":"Li","year":"2024","journal-title":"Exp. Gerontol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"111588","DOI":"10.1016\/j.exger.2021.111588","article-title":"Senolytics and the compression of late-life mortality","volume":"155","author":"Kowald","year":"2021","journal-title":"Exp. Gerontol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.cmet.2020.04.001","article-title":"Benefits of Metformin in Attenuating the Hallmarks of Aging","volume":"32","author":"Kulkarni","year":"2020","journal-title":"Cell Metab."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"111350","DOI":"10.1016\/j.mad.2020.111350","article-title":"Is metformin a geroprotector? A peek into the current clinical and experimental data","volume":"191","author":"Zajda","year":"2020","journal-title":"Mech. Ageing Dev."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1007\/s00125-017-4342-z","article-title":"The mechanisms of action of metformin","volume":"60","author":"Rena","year":"2017","journal-title":"Diabetologia"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1007\/s13340-016-0300-0","article-title":"Metformin: Clinical topics and new mechanisms of action","volume":"8","author":"Fujita","year":"2017","journal-title":"Diabetol. Int."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"294","DOI":"10.3389\/fendo.2019.00294","article-title":"Role of Mitochondria in the Mechanism(s) of Action of Metformin","volume":"10","author":"Vial","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Mohammed, I., Hollenberg, M.D., Ding, H., and Triggle, C.R. (2021). A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.718942"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"6358","DOI":"10.1016\/j.cell.2024.08.021","article-title":"Metformin decelerates aging clock in male monkeys","volume":"187","author":"Yang","year":"2024","journal-title":"Cell"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"e13122","DOI":"10.1111\/acel.13122","article-title":"The JAK1\/2 inhibitor ruxolitinib delays premature aging phenotypes","volume":"19","author":"Griveau","year":"2020","journal-title":"Aging Cell"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1111\/acel.12587","article-title":"Rapamycin inhibits the secretory phenotype of senescent cells by a Nrf2-independent mechanism","volume":"16","author":"Wang","year":"2017","journal-title":"Aging Cell"},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Luis, C., Maduro, A.T., Pereira, P., Mendes, J.J., Soares, R., and Ramalho, R. (2022). Nutritional senolytics and senomorphics: Implications to immune cells metabolism and aging\u2014from theory to practice. Front. Nutr., 9.","DOI":"10.3389\/fnut.2022.958563"},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Martin Gimenez, V.M., de Las Heras, N., Lahera, V., Tresguerres, J.A.F., Reiter, R.J., and Manucha, W. (2022). Melatonin as an Anti-Aging Therapy for Age-Related Cardiovascular and Neurodegenerative Diseases. Front. Aging Neurosci., 14.","DOI":"10.3389\/fnagi.2022.888292"},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Cruciani, S., Garroni, G., Pala, R., Barcessat, A.R.P., Facchin, F., Ventura, C., Fozza, C., and Maioli, M. (2022). Melatonin finely tunes proliferation and senescence in hematopoietic stem cells. Eur. J. Cell Biol., 101.","DOI":"10.1016\/j.ejcb.2022.151251"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1186\/s13287-021-02322-9","article-title":"Melatonin induces the rejuvenation of long-term ex vivo expanded periodontal ligament stem cells by modulating the autophagic process","volume":"12","author":"Tan","year":"2021","journal-title":"Stem Cell Res. Ther."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1089\/ars.2009.2876","article-title":"Superoxide dismutase mimics: Chemistry, pharmacology, and therapeutic potential","volume":"13","author":"Reboucas","year":"2010","journal-title":"Antioxid. Redox Signal"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.bmc.2016.10.018","article-title":"New glutathione peroxidase mimetics-Insights into antioxidant and cytotoxic activity","volume":"25","author":"Pacula","year":"2017","journal-title":"Bioorganic Med. Chem."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"5642148","DOI":"10.1155\/2018\/5642148","article-title":"Sulforaphane Delays Fibroblast Senescence by Curbing Cellular Glucose Uptake, Increased Glycolysis, and Oxidative Damage","volume":"2018","author":"Hariton","year":"2018","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Liao, K.M., Chen, C.J., Luo, W.J., Hsu, C.W., Yu, S.L., Yang, P.C., and Su, K.Y. (2023). Senomorphic effect of diphenyleneiodonium through AMPK\/MFF\/DRP1 mediated mitochondrial fission. Biomed. Pharmacother., 162.","DOI":"10.1016\/j.biopha.2023.114616"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1089\/ars.2013.5814","article-title":"Evolution of NADPH Oxidase Inhibitors: Selectivity and Mechanisms for Target Engagement","volume":"23","author":"Altenhofer","year":"2015","journal-title":"Antioxid. Redox Signal"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"7274","DOI":"10.18632\/oncotarget.23752","article-title":"A novel suicide gene therapy for the treatment of p16(Ink4a)-overexpressing tumors","volume":"9","author":"Kohli","year":"2018","journal-title":"Oncotarget"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"518","DOI":"10.18632\/aging.101422","article-title":"Gene therapy for p16-overexpressing cells","volume":"10","author":"Demaria","year":"2018","journal-title":"Aging"},{"key":"ref_145","first-page":"1865","article-title":"The flavonoid, fisetin, inhibits UV radiation-induced oxidative stress and the activation of NF-\u03baB and MAPK signaling in human lens epithelial cells","volume":"14","author":"Yao","year":"2008","journal-title":"Mol. Vis."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1002\/cbdv.201500060","article-title":"Luteolin Supplementation Prevents Selenite-Induced Cataractogenesis in Sprague Dawley Rat Pups","volume":"12","author":"Sreelakshmi","year":"2015","journal-title":"Chem. Biodivers."},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Chhunchha, B., Kubo, E., and Singh, D.P. (2022). Obligatory Role of AMPK Activation and Antioxidant Defense Pathway in the Regulatory Effects of Metformin on Cellular Protection and Prevention of Lens Opacity. Cells, 11.","DOI":"10.3390\/cells11193021"},{"key":"ref_148","first-page":"8","article-title":"Metformin protects lens epithelial cells against senescence in a naturally aged mouse model","volume":"8","author":"Chen","year":"2022","journal-title":"Cell Death Discov."},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Mi, Y., Wei, C., Sun, L., Liu, H., Zhang, J., Luo, J., Yu, X., He, J., Ge, H., and Liu, P. (2023). Melatonin inhibits ferroptosis and delays age-related cataract by regulating SIRT6\/p-Nrf2\/GPX4 and SIRT6\/NCOA4\/FTH1 pathways. Biomed. Pharmacother., 157.","DOI":"10.1016\/j.biopha.2022.114048"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/2\/244\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:31:42Z","timestamp":1760027502000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/2\/244"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,12]]},"references-count":149,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["ph18020244"],"URL":"https:\/\/doi.org\/10.3390\/ph18020244","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,12]]}}}