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We aimed to explore whether iron is involved in the pathogenesis role of senescence in DN.\u00a0Renal cells were treated with high glucose (HG, 35\u2009mM) for 10 or 15 days, and DN mice were induced by high\u2010fat diet and streptozotocin. Gene ontology enrichment, gene set enrichment analysis analysis, \u03b2\u2010galactosidase staining, 5\u2010ethynyl\u20102\u2010deoxyuridine staining, and western blot depicted the upregulated senescence pathway in vitro and in vivo of DN. Lactate dehydrogenase (LDH) release was increased by HG and reversed by p16\/p21 knockdown, and the supernatant of HG\u2010treated cells caused increased LDH release from normal cells. Iron metabolism\u2010related protein expression was disordered after HG exposure concomitant with senescence. Ferric ammonium citrate (50\u2009\u03bcM) upregulated gamma\u2010H2A.X variant histone and\u00a0increased the senescence markers in HG\u2010treated cells. The treatment of deferoxamine (0.5\u2009\u03bcM) had the opposite effect. Compared to the non\u2010DN individual, increased ferritin and senescence markers were verified in DN mice and patients, and the co\u2010localization of ferritin and senescence markers was observed by immunofluorescence. These results suggested that accumulated iron was correlated with aggravated DNA damage and accelerated senescence, and revealed the role of iron in the cellular senescence of diseases.<\/jats:p>","DOI":"10.1002\/jbt.23683","type":"journal-article","created":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T12:31:16Z","timestamp":1710419476000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Excess iron accumulation mediated senescence in diabetic kidney injury"],"prefix":"10.1002","volume":"38","author":[{"given":"Xueer","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Nutrition and Food Hygiene, Key Laboratory of Environment &amp; Health, Ministry of Education Huazhong University of Science and Technology Wuhan China"},{"name":"Department of Nutrition and Food Hygiene, State Environment of Protection Key Laboratory of Health Effects of Environmental Pollution Huazhong University of Science and Technology Wuhan China"},{"name":"Department of Nutrition and Food Hygiene, State Key Laboratory of Environment Health (Incubation) Huazhong University of Science and Technology Wuhan China"},{"name":"Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Teaching and Research Shenzhen Center for Chronic Disease Control Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, Key Laboratory of Environment &amp; 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