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In search for the long\u2010term beneficial or adverse effects of antidiabetic vanadyl complexes, we serendipitously discovered that the vanadyl complexes VOp\u2010dmada exerted pro\u2010healthy aging effects across a diverse panel of model organisms, i.e., yeast,\n                    <jats:italic>C. elegans<\/jats:italic>\n                    , and SAMP8 mice. Furthermore, VOp\u2010dmada attenuated replicative senescence in mouse embryonic fibroblasts and alleviated thymic epithelial cell aging while preserving thymic architecture and function in a mouse model of dexamethasone\u2010induced acute thymic atrophy. Mechanistic investigations revealed that VOp\u2010dmada improved the structural integrity and functional capacity of mitochondrial complex II. This effect was mediated by activation of the c\u2010Myc\/S\u2010phase kinase\u2010associated protein 2 (SKP2)\/sirtuin 3 (SIRT3) signaling axis, which in turn upregulated succinate dehydrogenase subunit A (SDHA) expression. Thus, vanadyl complexes suppressed reactive oxygen species (ROS) generation at the source, disrupted the deleterious ROS\u2013thioredoxin\u2010interacting protein (TXNIP) vicious cycle, and ultimately decelerated the aging process. Our findings highlight the potential application of antidiabetic vanadium complexes in the treatment of other aging\u2010related disorders and corroborate the chronic safety profile. Moreover, these results support the targeting of mitochondrial complex II function and integrity as a novel strategy for the discovery of pro\u2010healthy aging agents.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.202600003","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T15:32:37Z","timestamp":1774539157000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Vanadyl Complexes (VOp\u2010Dmada) Promote Healthy Aging by Regulating Electron Transport Mediated by Mitochondrial Complex II"],"prefix":"10.1002","volume":"21","author":[{"given":"Jiayu","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Natural and Biomimetic Drugs and Department of Chemical Biology School of Pharmaceutical Sciences Peking University Health Science Center  Beijing 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