Artificially stimulating retrotransposon activity increases mortality and accelerates a subset of aging phenotypes in Drosophila

Abstract

Transposable elements (TE) are mobile sequences of DNA that can become transcriptionally active as an animal ages. Whether TE activity is simply a byproduct of heterochromatin breakdown or can contribute towards the aging process is not known. Here we place the TE gypsy under the control of the UAS GAL4 system to model TE activation during aging. We find that increased TE activity shortens the lifespan of male D. melanogaster. The effect is only apparent in middle aged animals. The increase in mortality is not seen in young animals. An intact reverse transcriptase is necessary for the decrease in lifespan implicating a DNA mediated process in the effect. The decline in lifespan in the active gypsy flies is accompanied by the acceleration of a subset of aging phenotypes. TE activity increases sensitivity to oxidative stress and promotes a decline in circadian rhythmicity. The overexpression of the Forkhead-box O family (FOXO) stress response transcription factor can partially rescue the detrimental effects of increased TE activity on lifespan. Our results provide evidence that active TEs can behave as effectors in the aging process and suggest a potential novel role for dFOXO in its promotion of longevity in D. melanogaster.

Data availability

Sequencing data have been deposited in GEO under accession code GSE205416.

The following data sets were generated

Article and author information

Author details

  1. Joyce Rigal

    Department of Biology, Brandeis University, Waltham, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Ane Martin Anduaga

    Department of Biology, Brandeis University, Waltham, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2447-2195
  3. Elena Bitman

    Department of Biology, Brandeis University, Waltham, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Emma Rivellese

    Department of Biology, Brandeis University, Waltham, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Sebastian Kadener

    Department of Biology, Brandeis University, Waltham, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0080-5987
  6. Michael T Marr II

    Department of Biology, Brandeis University, Waltham, United States
    For correspondence
    mmarr@brandeis.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7366-7987

Funding

National Institute on Aging (R21AG054724)

  • Joyce Rigal
  • Michael T Marr II

National Institute on Aging (R01AG057700)

  • Sebastian Kadener
  • Michael T Marr II

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

Copyright

© 2022, Rigal 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. Joyce Rigal
  2. Ane Martin Anduaga
  3. Elena Bitman
  4. Emma Rivellese
  5. Sebastian Kadener
  6. Michael T Marr II
(2022)
Artificially stimulating retrotransposon activity increases mortality and accelerates a subset of aging phenotypes in Drosophila
eLife 11:e80169.
https://doi.org/10.7554/eLife.80169

Share this article

https://doi.org/10.7554/eLife.80169

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