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

Iole Ferrara-Romeo, Paula Martinez, Sarita Saraswati, Kurt Whittemore, Osvaldo Graña-Castro, Lydia Thelma Poluha, Rosa Serrano, Elena Hernandez-Encinas, Carmen Blanco-Aparicio, Juana Maria Flores and Maria A. Blasco ()
Additional contact information
Iole Ferrara-Romeo: Spanish National Cancer Centre (CNIO)
Paula Martinez: Spanish National Cancer Centre (CNIO)
Sarita Saraswati: Spanish National Cancer Centre (CNIO)
Kurt Whittemore: Spanish National Cancer Centre (CNIO)
Osvaldo Graña-Castro: Spanish National Cancer Centre (CNIO)
Lydia Thelma Poluha: Spanish National Cancer Centre (CNIO)
Rosa Serrano: Spanish National Cancer Centre (CNIO)
Elena Hernandez-Encinas: Spanish National Cancer Centre (CNIO)
Carmen Blanco-Aparicio: Spanish National Cancer Centre (CNIO)
Juana Maria Flores: Complutense University of Madrid
Maria A. Blasco: Spanish National Cancer Centre (CNIO)

Nature Communications, 2020, vol. 11, issue 1, 1-17

Abstract: 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.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-14962-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14962-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-14962-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().