Endothelial progeria induces adipose tissue senescence and impairs insulin sensitivity through senescence associated secretory phenotype.

ABSTRACT: Vascular senescence is thought to play a crucial role in an ageing-associated decline of organ functions; however, whether vascular senescence is causally implicated in age-related disease remains unclear. Here we show that endothelial cell (EC) senescence induces metabolic disorders through the senescence-associated secretory phenotype. Senescence-messaging secretomes from senescent ECs induced a senescence-like state and reduced insulin receptor substrate-1 in adipocytes, which thereby impaired insulin signaling. We generated EC-specific progeroid mice that overexpressed the dominant negative form of telomeric repeat-binding factor 2 under the control of the Tie2 promoter. EC-specific progeria impaired systemic metabolic health in mice in association with adipose tissue dysfunction even

SUBMITTER: Barinda AJ 

PROVIDER: S-EPMC6981212 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature