2026-08-29T14:15:04Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/97252024-11-29T14:57:49Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
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
funder
Ministerio de Economía y Competitividad (España)
funder
Comunidad de Madrid (España)
funder
World Cancer Research Fund International
funder
Botín Foundation
2020-04-23T16:13:47Z
2020-04-23T16:13:47Z
2020-03-03
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
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.
eng
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
journal article
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