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.

Details

Title
Promoting Drp1-mediated mitochondrial fission in midlife prolongs healthy lifespan of Drosophila melanogaster
Author
Rana, Anil 1 ; Oliveira, Matheus P 2 ; Khamoui, Andy V 3 ; Aparicio, Ricardo 1 ; Rera, Michael 4   VIAFID ORCID Logo  ; Rossiter, Harry B 5   VIAFID ORCID Logo  ; Walker, David W 6 

1  Department of Integrative Biology and Physiology, University of California, Los Angeles, CA, USA 
2  Department of Integrative Biology and Physiology, University of California, Los Angeles, CA, USA; Instituto de Bioquimica Medica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil 
3  Division of Respiratory & Critical Care Physiology & Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA; Department of Exercise Science and Health Promotion, Florida Atlantic University, Boca Raton, FL, USA 
4  Department of Integrative Biology and Physiology, University of California, Los Angeles, CA, USA; Laboratory of Degenerative Processes, Stress and Aging, Université Paris Diderot, Paris, France 
5  Division of Respiratory & Critical Care Physiology & Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA; Faculty of Biological Sciences, University of Leeds, Leeds, UK 
6  Department of Integrative Biology and Physiology, University of California, Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles, CA, USA 
Pages
1-14
Publication year
2017
Publication date
Sep 2017
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-017-00525-4
ProQuest document ID
1936207668
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.