2026-08-29T14:15:08Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/97252024-11-29T14:57:49Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Ferrara Romeo, Iole author Martinez Rodriguez, Paula author Saraswati, Sarita author Whittemore, Kurt author Graña Castro, Osvaldo author Thelma Poluha, Lydia author Serrano Ruiz, Rosa author Hernandez-Encinas, Elena author Blanco-Aparicio, Carmen author Maria Flores, Juana author Blasco , MA author 2020-03-03 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. Nat Commun. 2020 ;11(1):1168 10.1038/s41467-020-14962-1 2041-1723 2041-1723 Nature communications 32127537 http://hdl.handle.net/20.500.12105/9725 EXTENDS LIFE-SPAN TUBEROUS SCLEROSIS MAMMALIAN TARGET RAPAMYCIN S6 KINASE PROTEIN GENE CANCER EXPRESSION LENGTH The mTOR pathway is necessary for survival of mice with short telomeres