The mTOR pathway is necessary for survival of mice with short telomeres.

ABSTRACT: Telomerase deficiency leads to age-related diseases and shorter lifespans. Inhibition of the mechanistic target of rapamycin (mTOR) delays aging and age-related pathologies. Here, we show that telomerase deficient mice with short telomeres (G2-Terc^-/-) have an hyper-activated mTOR pathway with increased levels of phosphorylated ribosomal S6 protein in liver, skeletal muscle and heart, a target of mTORC1. Transcriptional profiling confirms mTOR activation in G2-Terc^-/- livers. Treatment of G2-Terc^-/- mice with rapamycin, an inhibitor of mTORC1, decreases survival, in contrast to lifespan extension in wild-type controls. Deletion of mTORC1 downstream S6 kinase 1 in G3-Terc^-/- mice also decreases longevity, in contrast to lifespan extension in singl

SUBMITTER: Ferrara-Romeo I 

PROVIDER: S-EPMC7054554 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature