Reactivation of RNA metabolism underlies somatic restoration after adult reproductive diapause in C. elegans

Abstract

The mechanisms underlying biological aging are becoming recognized as therapeutic targets to delay the onset of multiple age-related morbidities. Even greater health benefits can potentially be achieved by halting or reversing age-associated changes. C. elegans restore their tissues and normal longevity upon exit from prolonged adult reproductive diapause, but the mechanisms underlying this phenomenon remain unknown. Here, we focused on the mechanisms controlling recovery from adult diapause. Here, we show that functional improvement of post-mitotic somatic tissues does not require germline signaling, germline stem cells, or replication of nuclear or mitochondrial DNA. Instead a large expansion of the somatic RNA pool is necessary for restoration of youthful function and longevity. Treating animals with the drug 5-fluoro-2'-deoxyuridine prevents this restoration by blocking reactivation of RNA metabolism. These observations define a critical early step during exit from adult reproductive diapause that is required for somatic rejuvenation of an adult metazoan animal.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Nikolay Burnaevskiy

    Department of Pathology, University of Washington, Seattle, United States
    Competing interests
    No competing interests declared.
  2. Shengying Chen

    Department of Pathology, University of Washington, Seattle, United States
    Competing interests
    No competing interests declared.
  3. Miguel Mailig

    Department of Pathology, University of Washington, Seattle, United States
    Competing interests
    No competing interests declared.
  4. Anthony Reynolds

    Department of Pathology, University of Washington, Seattle, United States
    Competing interests
    No competing interests declared.
  5. Shruti Karanth

    Department of Pathology, University of Washington, Seattle, United States
    Competing interests
    No competing interests declared.
  6. Alexander Mendenhall

    Department of Pathology, University of Washington, Seattle, United States
    Competing interests
    No competing interests declared.
  7. Marc Van Gilst

    Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, United States
    Competing interests
    No competing interests declared.
  8. Matt Kaeberlein

    Department of Pathology, University of Washington, Seattle, United States
    For correspondence
    kaeber@uw.edu
    Competing interests
    Matt Kaeberlein, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1311-3421

Funding

National Institute on Aging (T32AG000057)

  • Nikolay Burnaevskiy

National Institute on Aging (R01AG031108)

  • Matt Kaeberlein

National Institute on Aging (R00AG045341)

  • Alexander Mendenhall

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Gary Ruvkun, Massachusetts General Hospital, United States

Publication history

  1. Received: February 24, 2018
  2. Accepted: August 1, 2018
  3. Accepted Manuscript published: August 2, 2018 (version 1)
  4. Version of Record published: August 13, 2018 (version 2)

Copyright

© 2018, Burnaevskiy et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Nikolay Burnaevskiy
  2. Shengying Chen
  3. Miguel Mailig
  4. Anthony Reynolds
  5. Shruti Karanth
  6. Alexander Mendenhall
  7. Marc Van Gilst
  8. Matt Kaeberlein
(2018)
Reactivation of RNA metabolism underlies somatic restoration after adult reproductive diapause in C. elegans
eLife 7:e36194.
https://doi.org/10.7554/eLife.36194

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