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Apoptosis of lens epithelial cells (LECs) is the important cellular basis of senile cataract resulted from prolonged exposure to oxidative stress, although the specific mechanisms remain elusive. Our data indicated the concomitance of high autophagy activity, low SQSTM1\/p62 protein level and apoptosis in the same LEC from senile cataract patients. Meanwhile, in primary cultured LECs model, more durable autophagy activation and more obvious p62 degradation under oxidative stress were observed in LECs from elder healthy donors, compared with that from young healthy donors. Using autophagy-deficiency HLE-B3 cell line, autophagy adaptor p62 was identified as the critical scaffold protein sustaining the pro-survival signaling PKC\u03b9-IKK-NF-\u03baB cascades, which antagonized the pro-apoptotic signaling. Moreover, the pharmacological inhibitor of autophagy, 3-MA, significantly inhibited p62 degradation and rescued oxidative stress-induced apoptosis in elder LECs. Collectively, this study demonstrated that durable activation of autophagy promoted age-related cell death in LECs. Our work contributes to better understanding the pathogenesis of senescence-associated diseases.<\/jats:p>","DOI":"10.1038\/s41419-021-04489-8","type":"journal-article","created":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T07:04:21Z","timestamp":1641798261000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Autophagy facilitates age-related cell apoptosis\u2014a new insight from senile cataract"],"prefix":"10.1038","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3796-0737","authenticated-orcid":false,"given":"Jiani","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wangshu","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6140-9633","authenticated-orcid":false,"given":"Xiaoying","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2339-5741","authenticated-orcid":false,"given":"Wei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1696-0615","authenticated-orcid":false,"given":"Wei","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,1,10]]},"reference":[{"key":"4489_CR1","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1038\/s41586-019-1365-2","volume":"571","author":"J Campisi","year":"2019","unstructured":"Campisi J, Kapahi P, Lithgow GJ, Melov S, Newman JC, Verdin E. 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