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Cell senescence results in part from inactivation of telomerase (TERT). Here, we analyzed mice with <jats:italic>Tert<\/jats:italic> knockout specifically in EC. <jats:italic>Tert<\/jats:italic> loss in EC induced transcriptional changes indicative of senescence and tissue hypoxia in EC and in other cells. We demonstrate that EC\u2010<jats:italic>Tert<\/jats:italic>\u2010KO mice have leaky blood vessels. The blood\u2013brain barrier of EC\u2010<jats:italic>Tert<\/jats:italic>\u2010KO mice is compromised, and their cognitive function is impaired. EC\u2010<jats:italic>Tert<\/jats:italic>\u2010KO mice display reduced muscle endurance and decreased expression of enzymes responsible for oxidative metabolism. Our data indicate that <jats:italic>Tert<\/jats:italic>\u2010KO EC have reduced mitochondrial content and function, which results in increased dependence on glycolysis. Consistent with this, EC\u2010<jats:italic>Tert<\/jats:italic>\u2010KO mice have metabolism changes indicative of increased glucose utilization. In EC\u2010<jats:italic>Tert<\/jats:italic>\u2010KO mice, expedited telomere attrition is observed for EC of adipose tissue (AT), while brain and skeletal muscle EC have normal telomere length but still display features of senescence. Our data indicate that the loss of <jats:italic>Tert<\/jats:italic> causes EC senescence in part through a telomere length\u2010independent mechanism undermining mitochondrial function. We conclude that EC\u2010<jats:italic>Tert<\/jats:italic>\u2010KO mice is a model of expedited vascular senescence recapitulating the hallmarks aging, which can be useful for developing revitalization therapies.<\/jats:p>","DOI":"10.1111\/acel.14138","type":"journal-article","created":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T05:39:15Z","timestamp":1710308355000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Endothelial\u2010specific telomerase inactivation causes telomere\u2010independent cell senescence and multi\u2010organ dysfunction characteristic of aging"],"prefix":"10.1111","volume":"23","author":[{"given":"Zhanguo","family":"Gao","sequence":"first","affiliation":[{"name":"The Brown Foundation Institute of Molecular Medicine University of Texas Health Science Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael 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