Endothelial-specific telomerase inactivation causes telomere-independent cell senescence and multi-organ dysfunction characteristic of aging.

ABSTRACT: It has remained unclear how aging of endothelial cells (EC) contributes to pathophysiology of individual organs. Cell senescence results in part from inactivation of telomerase (TERT). Here, we analyzed mice with Tert knockout specifically in EC. Tert loss in EC induced transcriptional changes indicative of senescence and tissue hypoxia in EC and in other cells. We demonstrate that EC-Tert-KO mice have leaky blood vessels. The blood-brain barrier of EC-Tert-KO mice is compromised, and their cognitive function is impaired. EC-Tert-KO mice display reduced muscle endurance and decreased expression of enzymes responsible for oxidative metabolism. Our data indicate that Tert-KO EC have reduced mitochondrial content and function, which results in increased dependence on glycolysis. Consistent wi

SUBMITTER: Gao Z 

PROVIDER: S-EPMC11296101 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature