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dc.contributor.author | Ferrara Romeo, Iole | |
dc.contributor.author | Martinez Rodriguez, Paula | |
dc.contributor.author | Saraswati, Sarita | |
dc.contributor.author | Whittemore, Kurt | |
dc.contributor.author | Graña Castro, Osvaldo | |
dc.contributor.author | Thelma Poluha, Lydia | |
dc.contributor.author | Serrano Ruiz, Rosa | |
dc.contributor.author | Hernandez-Encinas, Elena | |
dc.contributor.author | Blanco-Aparicio, Carmen | |
dc.contributor.author | Maria Flores, Juana | |
dc.contributor.author | Blasco , MA | |
dc.date.accessioned | 2020-04-23T16:13:47Z | |
dc.date.available | 2020-04-23T16:13:47Z | |
dc.date.issued | 2020-03-03 | |
dc.identifier.citation | Nat Commun. 2020 ;11(1):1168 | es_ES |
dc.identifier.issn | 2041-1723 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/9725 | |
dc.description.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. | es_ES |
dc.description.sponsorship | We thank Sara Kozma for kindly sharing the S6K1-/- mouse. We thank A. Efeyan and A. Ortega for helpful discussions. We are indebted to D. Megias for confocal microscopy analysis. Research in the Blasco Lab is funded by the Spanish Ministry of Economy and Competitiveness Projects (SAF2013-45111-R and SAF2015-72455-EXP), the Comunidad de Madrid Project (S2017/BMD-3770), the World Cancer Research (WCR) Project (16-1177), and the Fundacion Botin (Spain). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Nature Publishing Group | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | * |
dc.subject | EXTENDS LIFE-SPAN | es_ES |
dc.subject | TUBEROUS SCLEROSIS | es_ES |
dc.subject | MAMMALIAN TARGET | es_ES |
dc.subject | RAPAMYCIN | es_ES |
dc.subject | S6 KINASE | es_ES |
dc.subject | PROTEIN | es_ES |
dc.subject | GENE | es_ES |
dc.subject | CANCER | es_ES |
dc.subject | EXPRESSION | es_ES |
dc.subject | LENGTH | es_ES |
dc.title | The mTOR pathway is necessary for survival of mice with short telomeres | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución-NoComercial-CompartirIgual 4.0 Internacional | * |
dc.identifier.pubmedID | 32127537 | es_ES |
dc.format.volume | 11 | es_ES |
dc.format.number | 1 | es_ES |
dc.format.page | 1168 | es_ES |
dc.identifier.doi | 10.1038/s41467-020-14962-1 | es_ES |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | |
dc.contributor.funder | Comunidad de Madrid (España) | |
dc.contributor.funder | World Cancer Research Fund International | |
dc.contributor.funder | Botín Foundation | |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 2041-1723 | es_ES |
dc.relation.publisherversion | https://doi.org/10.1038/s41467-020-14962-1. | es_ES |
dc.identifier.journal | Nature communications | es_ES |
dc.repisalud.institucion | CNIO | es_ES |
dc.repisalud.orgCNIO | CNIO::Grupos de investigación::Grupo de Telómeros y Telomerasa | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/SAF2015-72455-EXP | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/SAF2013-45111-R | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/S2017/BMD-3770 | es_ES |
dc.rights.accessRights | open access | es_ES |