Rapamycin increases oxidative metabolism and enhances metabolic flexibility in human cardiac fibroblasts.

ABSTRACT: Inhibition of mTOR signaling using rapamycin has been shown to increase lifespan and healthspan in multiple model organisms; however, the precise mechanisms for the beneficial effects of rapamycin remain uncertain. We have previously reported that rapamycin delays senescence in human cells and that enhanced mitochondrial biogenesis and protection from mitochondrial stress is one component of the benefit provided by rapamycin treatment. Here, using two models of senescence, replicative senescence and senescence induced by the presence of the Hutchinson-Gilford progeria lamin A mutation, we report that senescence is accompanied by elevated glycolysis and increased oxidative phosphorylation, which are both reduced by rapamycin. Measurements of mitochondrial function indicate that direct mitoc

SUBMITTER: Nacarelli T 

PROVIDER: S-EPMC6060207 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature