{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T17:19:31Z","timestamp":1786123171902,"version":"build-2736575974"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"vor","delay-in-days":218,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Chronic oxidative stress has long been implicated in renal pathologies, but whether sustained oxidative damage primarily promotes chronic kidney disease (CKD) or tumorigenesis remains unclear. To address this question, we investigated the long\u2010term effects of oxidative stress on human embryonic kidney (HEK293T) cells chronically exposed to a low dose of hydrogen peroxide (H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    , 50\u2009\u03bcM H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    ) for 9 months, generating two adapted lines, 50R30 and 50R45. These cells exhibited enhanced survival and tolerance to acute high\u2010dose H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    challenge, indicating an oxidative stress\u2010resistant phenotype. Despite this adaptation, both cell lines showed markedly reduced proliferation and migration, reflecting loss of cellular vitality and function typical of renal degeneration. Transcriptomic and protein analyses revealed upregulation of genes and proteins involved in cell\u2010cycle arrest (p53 and p21), senescence, and the NF\u2010\u03baB\/IL\u20106\u2010driven senescence\u2010associated secretory phenotype (SASP), oxidative stress responses, together with elevated heat shock factor 1 (HSF1) expression indicative of biomolecular damage and impaired adaptive capacity. Collectively, these findings suggest that chronic oxidative stress drives cellular aging and dysfunction rather than malignant transformation, leading to degenerative changes resembling CKD pathology. Moreover, prolonged oxidative stress alone appears insufficient to induce carcinogenic transformation; additional genetic or epigenetic alterations, together with specific cellular machinery, are likely required to drive kidney malignancy. This study therefore provides mechanistic insight into how sustained oxidative stress promotes renal cell senescence and contributes to CKD progression.\n                  <\/jats:p>","DOI":"10.1155\/omcl\/3094707","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T14:00:42Z","timestamp":1786111242000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prolonged Oxidative Stress Drives p53\/p21\u2010Mediated Senescence and Degenerative Adaptation in Kidney\u2010Derived 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