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Optogenetic rejuvenation of mitochondrial membrane potential extends C. elegans lifespan

Nature Aging volume 3, pages 157–161 (2023)Cite this article

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Abstract

Mitochondrial dysfunction plays a central role in aging but the exact biological causes are still being determined. Here, we show that optogenetically increasing mitochondrial membrane potential during adulthood using a light-activated proton pump improves age-associated phenotypes and extends lifespan in Caenorhabditis elegans. Our findings provide direct causal evidence that rescuing the age-related decline in mitochondrial membrane potential is sufficient to slow the rate of aging and extend healthspan and lifespan.

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Fig. 1: Mitochondria-ON increased ∆ψm in vivo.
Fig. 2: mtON extended lifespan and healthspan.

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Data availability

All other data supporting the findings of this study are available from the corresponding author upon reasonable request. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org) via the PRIDE27,28,29 partner repository with the dataset identifier PXD033901.

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Acknowledgements

B.J.B. is supported by the Biological Mechanisms for Healthy Aging Training Grant National Institutes of Health (NIH)/National Institute on Aging T32 AG066574 and by NIH/NIA grant P30AG013280 to M.K. A.P.W. is supported by NIH grants (R01 NS092558 and R01 NS115906). S.P. is supported by a Deutsche Forschungsgemeinschaft grant (458246576) by two Longevity Impetus grants from Norn Group. We also acknowledge the W. M. Keck Microscopy Center and the Keck Center Manager and N. Peters for confocal microscopy access and training (NIH S10 OD016240).

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Authors and Affiliations

  1. University of Washington, Department of Laboratory Medicine & Pathology, Seattle, WA, USA

    Brandon J. Berry & Matt Kaeberlein

  2. University of Rochester Medical Center, Department of Anesthesiology and Perioperative Medicine, Rochester, NY, USA

    Anežka Vodičková & Andrew P. Wojtovich

  3. Research Group Epigenetics, Metabolism and Longevity, Research Institute for Farm Animal Biology (FBN), Dummerstorf, Germany

    Annika Müller-Eigner & Shahaf Peleg

  4. Bavarian Center for Biomolecular Mass Spectrometry (BayBioMS), Technical University of Munich, Freising, Germany

    Chen Meng & Christina Ludwig

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  1. Brandon J. Berry
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Contributions

B.J.B., M.K., S.P. and A.P.W. designed the research. B.J.B. performed the lifespans, imaging and analysis, healthspan experiments and data analysis. A.V. carried out lifespan and respiration experiments. A.M.E. carried out lifespan experiments. C.M. and C.L. carried out mass spectrometry. B.J.B. wrote the manuscript with input from M.K., S.P. and A.P.W.

Corresponding authors

Correspondence to Shahaf Peleg or Andrew P. Wojtovich.

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Competing interests

B.J.B., S.P. and A.P.W. are listed as inventors on a patent application based on some of the work described here. The remaining authors declare no competing interests.

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Nature Aging thanks Liza Pon, Alex Soukas, and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

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Supplementary Figs. 1–6 and Supplementary Tables 1–3.

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Figure 1

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Berry, B.J., Vodičková, A., Müller-Eigner, A. et al. Optogenetic rejuvenation of mitochondrial membrane potential extends C. elegans lifespan. Nat Aging 3, 157–161 (2023). https://doi.org/10.1038/s43587-022-00340-7

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