IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-020-14962-1.html
   My bibliography  Save this article

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

Author

Listed:
  • 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))

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.

Suggested Citation

  • 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 Fl, 2020. "The mTOR pathway is necessary for survival of mice with short telomeres," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14962-1
    DOI: 10.1038/s41467-020-14962-1
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-14962-1
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-020-14962-1?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Kan Xie & Helmut Fuchs & Enzo Scifo & Dan Liu & Ahmad Aziz & Juan Antonio Aguilar-Pimentel & Oana Veronica Amarie & Lore Becker & Patricia da Silva-Buttkus & Julia Calzada-Wack & Yi-Li Cho & Yushuang , 2022. "Deep phenotyping and lifetime trajectories reveal limited effects of longevity regulators on the aging process in C57BL/6J mice," Nature Communications, Nature, vol. 13(1), pages 1-29, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14962-1. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.