IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v6y2015i1d10.1038_ncomms7790.html
   My bibliography  Save this article

Controlled induction of DNA double-strand breaks in the mouse liver induces features of tissue ageing

Author

Listed:
  • Ryan R. White

    (Albert Einstein College of Medicine)

  • Brandon Milholland

    (Albert Einstein College of Medicine)

  • Alain de Bruin

    (Faculty of Veterinary Medicine, Dutch Molecular Pathology Center, Utrecht University)

  • Samuel Curran

    (Buck Institute for Research on Aging
    Present address: The Graduate Group in Comparative Biochemistry, University of California, Berkeley, Berkeley, CA 94720, USA)

  • Remi-Martin Laberge

    (Buck Institute for Research on Aging)

  • Harry van Steeg

    (National Institute of Public Health and the Environment (RIVM))

  • Judith Campisi

    (Buck Institute for Research on Aging
    Lawrence Berkeley National Laboratory)

  • Alexander Y. Maslov

    (Albert Einstein College of Medicine)

  • Jan Vijg

    (Albert Einstein College of Medicine)

Abstract

DNA damage has been implicated in ageing, but direct evidence for a causal relationship is lacking, owing to the difficulty of inducing defined DNA lesions in cells and tissues without simultaneously damaging other biomolecules and cellular structures. Here we directly test whether highly toxic DNA double-strand breaks (DSBs) alone can drive an ageing phenotype using an adenovirus-based system based on tetracycline-controlled expression of the SacI restriction enzyme. We deliver the adenovirus to mice and compare molecular and cellular end points in the liver with normally aged animals. Treated, 3-month-old mice display many, but not all signs of normal liver ageing as early as 1 month after treatment, including ageing pathologies, markers of senescence, fused mitochondria and alterations in gene expression profiles. These results, showing that DSBs alone can cause distinct ageing phenotypes in mouse liver, provide new insights in the role of DNA damage as a driver of tissue ageing.

Suggested Citation

  • Ryan R. White & Brandon Milholland & Alain de Bruin & Samuel Curran & Remi-Martin Laberge & Harry van Steeg & Judith Campisi & Alexander Y. Maslov & Jan Vijg, 2015. "Controlled induction of DNA double-strand breaks in the mouse liver induces features of tissue ageing," Nature Communications, Nature, vol. 6(1), pages 1-11, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7790
    DOI: 10.1038/ncomms7790
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms7790
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms7790?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
    ---><---

    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:6:y:2015:i:1:d:10.1038_ncomms7790. 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.