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Promoting Drp1-mediated mitochondrial fission in midlife prolongs healthy lifespan of Drosophila melanogaster

Author

Listed:
  • Anil Rana

    (University of California)

  • Matheus P. Oliveira

    (University of California
    Universidade Federal do Rio de Janeiro)

  • Andy V. Khamoui

    (Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
    Florida Atlantic University)

  • Ricardo Aparicio

    (University of California)

  • Michael Rera

    (University of California
    Université Paris Diderot)

  • Harry B. Rossiter

    (Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
    University of Leeds)

  • David W. Walker

    (University of California
    University of California)

Abstract

The accumulation of dysfunctional mitochondria has been implicated in aging, but a deeper understanding of mitochondrial dynamics and mitophagy during aging is missing. Here, we show that upregulating Drp1—a Dynamin-related protein that promotes mitochondrial fission—in midlife, prolongs Drosophila lifespan and healthspan. We find that short-term induction of Drp1, in midlife, is sufficient to improve organismal health and prolong lifespan, and observe a midlife shift toward a more elongated mitochondrial morphology, which is linked to the accumulation of dysfunctional mitochondria in aged flight muscle. Promoting Drp1-mediated mitochondrial fission, in midlife, facilitates mitophagy and improves both mitochondrial respiratory function and proteostasis in aged flies. Finally, we show that autophagy is required for the anti-aging effects of midlife Drp1-mediated mitochondrial fission. Our findings indicate that interventions that promote mitochondrial fission could delay the onset of pathology and mortality in mammals when applied in midlife.

Suggested Citation

  • Anil Rana & Matheus P. Oliveira & Andy V. Khamoui & Ricardo Aparicio & Michael Rera & Harry B. Rossiter & David W. Walker, 2017. "Promoting Drp1-mediated mitochondrial fission in midlife prolongs healthy lifespan of Drosophila melanogaster," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00525-4
    DOI: 10.1038/s41467-017-00525-4
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