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

Nature Communications
Iole Ferrara-RomeoMaria A Blasco

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 single S6K1-/- female mice. These findings demonstrate that mTOR is important for survival in the context of short telomeres, and that its inhibition is deleterious in this setting. These results are of clinical interest in the case of human syndromes characterized by critically short telomeres.

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Citations

Jul 1, 2020·International Journal of Molecular Sciences·Ekaterina ProshkinaAlexey Moskalev
Oct 11, 2020·GeroScience·Ramasamy SelvaraniArlan Richardson
Feb 9, 2021·Frontiers in Neuroscience·Sabrina ContinoPascal Kienlen-Campard
Jan 30, 2021·Cardiovascular Research·Sebastiano SciarrettaJunichi Sadoshima
Feb 23, 2021·Oncotarget·Mikhail V Blagosklonny
Mar 30, 2021·Oxidative Medicine and Cellular Longevity·Mingjing YanJian Li
Apr 4, 2021·International Journal of Molecular Sciences·Robert SolsonaAnthony Mj Sanchez
Apr 1, 2021·Rejuvenation Research·Mikhail V Blagosklonny

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Datasets Mentioned

BETA
GSE127475

Methods Mentioned

BETA
chromosomal aberrations
RNAseq
light microscopy
ELISA
Assay
Protein Assay
electrophoresis
PCR

Software Mentioned

TopHat
Analyst®
Gene Set Enrichment Analysis ( GSEA )
Definiens XD
FastQC
GSEAPreranked
Opera
AxioVision
GSEA
Analyst

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