{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:06:46Z","timestamp":1792033606208,"version":"4.4.0"},"reference-count":46,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:00:00Z","timestamp":1773964800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:00:00Z","timestamp":1773964800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82360435"],"award-info":[{"award-number":["82360435"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["85260435"],"award-info":[{"award-number":["85260435"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Intervertebral Disc Degeneration (IDD) is a common degenerative spinal disease and a leading cause of low back pain and disability. The senescence of nucleus pulposus cells (NPCs) is a central mechanism driving the pathological progression of IDD, though its regulatory mechanisms remain unclear. Bioinformatic analysis identified FGF21 as a key gene regulating NPCs senescence. In both human and rat degenerated intervertebral discs, FGF21 expression was significantly downregulated and closely associated with the upregulation of senescence markers (P16, P21, and P53) and clinical pathological features (age, symptom duration, and Pfirrmann grading). In\u00a0vitro experiments demonstrated that FGF21 intervention significantly alleviated tert\u2010butyl hydroperoxide (TBHP)\u2010induced NPCs senescence and mitochondrial damage. Mechanistically, FGF21 upregulated SIRT1 and promoted the deacetylation of FOXO3 at lysine sites K241, K258, K289, and K568, thereby enhancing mitophagy and inhibiting NPCs senescence. In\u00a0vivo, FGF21 treatment significantly improved disc height and histological scores in a rat IDD model, whereas SIRT1 knockdown attenuated these protective effects. In summary, FGF21 inhibits NPCs senescence and delays IDD progression by activating SIRT1\u2010mediated FOXO3 deacetylation and enhancing PINK1\u2010Parkin pathway\u2010dependent mitophagy. Therefore, the FGF21\u2010targeted SIRT1\/FOXO3\/PINK1\/Parkin axis may represent a promising new therapeutic strategy for IDD.<\/jats:p>","DOI":"10.1111\/acel.70449","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T15:34:21Z","timestamp":1774020861000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<scp>FGF21<\/scp>\n                    \u2010Mediated Upregulation of\n                    <scp>SIRT1<\/scp>\n                    Delays Intervertebral Disc Degeneration by Promoting\n                    <scp>PINK1<\/scp>\n                    \/Parkin Dependent Mitophagy Through Deacetylation of\n                    <scp>FOXO3<\/scp>"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8924-7311","authenticated-orcid":false,"given":"Zuo\u2010long","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Orthopedics Lanzhou University 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