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Vascular endothelial cells, which line blood vessels and directly contact blood flow, are susceptible to damage and play a key role in vascular aging; however, the underlying mechanisms of their aging remain unclear. Here, we identify TRPM7 as a key molecule in vascular endothelial aging. Endothelial deletion of TRPM7 significantly accelerates premature vascular aging in mice. Mechanistically, TRPM7 deficiency reduces lactate production and inhibits the lactylation writer protein p300, leading to decreased histone H3K18 lactylation. This induces a gene expression profile reprogramming, increasing the expression of the senescence gene p21 and decreasing the expression of angiogenesis genes. Inhibiting p21 or supplementing lactate reversed premature vascular endothelial aging caused by TRPM7 deficiency. This study reveals the critical role of the TRPM7\u2010H3K18la axis in vascular aging, offering potential therapeutic targets for vascular anti\u2010aging interventions.<\/jats:p>","DOI":"10.1111\/acel.70244","type":"journal-article","created":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T14:19:45Z","timestamp":1759414785000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["<scp>TRPM7<\/scp>\n                    Deficiency Accelerates Vascular Senescence by Inhibiting\n                    <scp>H3K18<\/scp>\n                    Lactylation"],"prefix":"10.1111","volume":"24","author":[{"given":"Yue","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Geriatric Medicine Xiangya Hospital, Central South University  Changsha People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Chen","sequence":"additional","affiliation":[{"name":"National 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