Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

Optogenetic rejuvenation of mitochondrial membrane potential extends C. elegans lifespan


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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

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

Similar content being viewed by others

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 ( via the PRIDE27,28,29 partner repository with the dataset identifier PXD033901.


  1. Lopez-Otin, C. et al. The hallmarks of aging. Cell 153, 1194–1217 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Berry, B. J. & Kaeberlein, M. An energetics perspective on geroscience: mitochondrial protonmotive force and aging. Geroscience 43, 1591–1604 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  3. Hughes, A. L. & Gottschling, D. E. An early age increase in vacuolar pH limits mitochondrial function and lifespan in yeast. Nature 492, 261–265 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Hughes, C. E. et al. Cysteine toxicity drives age-related mitochondrial decline by altering iron homeostasis. Cell 180, 296–310 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Mansell, E. et al. Mitochondrial potentiation ameliorates age-related heterogeneity in hematopoietic stem cell function. Cell Stem Cell (2020).

  6. Ziegler, D. V. et al. Calcium channel ITPR2 and mitochondria-ER contacts promote cellular senescence and aging. Nat. Commun. 12, 720 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Martínez-Reyes, I. & Chandel, N. S. Mitochondrial TCA cycle metabolites control physiology and disease. Nat. Commun. 11, 102 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  8. Waschuk, S. A. et al. Leptosphaeria rhodopsin: bacteriorhodopsin-like proton pump from a eukaryote. Proc. Natl Acad. Sci. USA 102, 6879–6883 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Berry, B. J. et al. Optogenetic control of mitochondrial protonmotive force to impact cellular stress resistance. EMBO Rep. 21, e49113 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. De Magalhaes Filho, C. D. et al. Visible light reduces C. elegans longevity. Nat. Commun. 9, 927 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Busack, I. et al. The OptoGenBox – a device for long-term optogenetics in. J. Neurogenet. 34, 466–474 (2020).

  12. Rea, S. L., Ventura, N. & Johnson, T. E. Relationship between mitochondrial electron transport chain dysfunction, development, and life extension in Caenorhabditis elegans. PLoS Biol. 5, e259 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  13. Ventura, N., Rea, S. L. & Testi, R. Long-lived C. elegans mitochondrial mutants as a model for human mitochondrial-associated diseases. Exp. Gerontol. 41, 974–991 (2006).

    Article  CAS  PubMed  Google Scholar 

  14. Yang, W. & Hekimi, S. A mitochondrial superoxide signal triggers increased longevity in Caenorhabditis elegans. PLoS Biol. 8, e1000556 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  15. Ristow, M. & Schmeisser, S. Extending life span by increasing oxidative stress. Free Radic. Biol. Med 51, 327–336 (2011).

    Article  CAS  PubMed  Google Scholar 

  16. Lee, S. S. et al. A systematic RNAi screen identifies a critical role for mitochondria in C. elegans longevity. Nat. Genet. 33, 40–48 (2003).

    Article  CAS  PubMed  Google Scholar 

  17. Glenn, C. F. et al. Behavioral deficits during early stages of aging in Caenorhabditis elegans result from locomotory deficits possibly linked to muscle frailty. J. Gerontol. A Biol. Sci. Med Sci. 59, 1251–1260 (2004).

    Article  PubMed  Google Scholar 

  18. Pelicioni, P. H. S. et al. Mild and marked executive dysfunction and falls in people with Parkinson’s disease. Braz. J Phys. Ther. (2020).

  19. Ibanez-Ventoso, C. et al. Automated analysis of C. elegans swim behavior using CeleST software. J. Vis. Exp. (2016).

  20. Burkewitz, K. et al. Neuronal CRTC-1 governs systemic mitochondrial metabolism and lifespan via a catecholamine signal. Cell 160, 842–855 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Philip, N. S. et al. Mos1 element-mediated CRISPR integration of transgenes in Caenorhabditis elegans. G3 9, 2629–2635 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Paix, A. et al. High efficiency, homology-directed genome editing in Caenorhabditis elegans using CRISPR-Cas9 ribonucleoprotein complexes. Genetics 201, 47–54 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Kwon, Y. J. et al. High-throughput biosorter quantification of relative mitochondrial content and membrane potential in living Caenorhabditis elegans. Mitochondrion 40, 42–50 (2018).

    Article  CAS  PubMed  Google Scholar 

  24. Tsalik, E. L. & Hobert, O. Functional mapping of neurons that control locomotory behavior in Caenorhabditis elegans. J. Neurobiol. 56, 178–197 (2003).

    Article  PubMed  Google Scholar 

  25. Berry, B. J. et al. Neuronal AMPK coordinates mitochondrial energy sensing and hypoxia resistance in C. elegans. FASEB J. 34, 16333–16347 (2020).

    Article  CAS  PubMed  Google Scholar 

  26. Cox, J. et al. Accurate proteome-wide label-free quantification by delayed normalization and maximal peptide ratio extraction, termed MaxLFQ. Mol. Cell Proteom. 13, 2513–2526 (2014).

    Article  CAS  Google Scholar 

  27. Perez-Riverol, Y. et al. The PRIDE database resources in 2022: a hub for mass spectrometry-based proteomics evidences. Nucleic Acids Res. 50, D543–D552 (2022).

    Article  CAS  PubMed  Google Scholar 

  28. Deutsch, E. W. et al. The ProteomeXchange consortium in 2020: enabling ‘big data’ approaches in proteomics. Nucleic Acids Res. 48, D1145–D1152 (2020).

    CAS  PubMed  Google Scholar 

  29. Perez-Riverol, Y. et al. PRIDE inspector toolsuite: moving toward a universal visualization tool for proteomics data standard formats and quality assessment of ProteomeXchange datasets. Mol. Cell Proteom. 15, 305–317 (2016).

    Article  CAS  Google Scholar 

Download references


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).

Author information

Authors and Affiliations



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.

Ethics declarations

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.

Peer review

Peer review information

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

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Information

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

Reporting Summary

Supplementary Data 1

Source data for Supplementary Fig. 2.

Supplementary Data 2

Source data for Supplementary Fig. 3.

Supplementary Data 3

Source data for Supplementary Fig. 5.

Supplementary Data 4

Source data for Supplementary Fig. 6.

Source data

Figure 1

Source data for Fig. 1.

Figure 2

Source data for Fig. 2.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing