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Nat Commun. 2017 Sep 6;8(1):448. doi: 10.1038/s41467-017-00525-4.

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

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Department of Integrative Biology and Physiology, University of California, Los Angeles, CA, 90095, USA.
Instituto de Bioquimica Medica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Cidade Universitaria, Rio de Janeiro, 21941-590, Brazil.
Division of Respiratory & Critical Care Physiology & Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
Department of Exercise Science and Health Promotion, Florida Atlantic University, Boca Raton, FL, 33431, USA.
Laboratory of Degenerative Processes, Stress and Aging, Université Paris Diderot, Paris, 75013, France.
Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK.
Department of Integrative Biology and Physiology, University of California, Los Angeles, CA, 90095, USA.
Molecular Biology Institute, University of California, Los Angeles, CA, 90095, USA.


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.Mitochondrial fission and fusion are important mechanisms to maintain mitochondrial function. Here, the authors report that middle-aged flies have more elongated, or 'hyper-fused' mitochondria, and show that induction of mitochondrial fission in midlife, but not in early life, extends the health and life of flies.

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