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Intermittent treatment with elamipretide preserves exercise tolerance in aged female mice

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Abstract

The pathology of aging impacts multiple organ systems, including the kidney and skeletal and cardiac muscles. Long-term treatment with the mitochondrial-targeted peptide elamipretide has previously been shown to improve in vivo mitochondrial function in aged mice, which is associated with increased fatigue resistance and treadmill performance, improved cardiovascular diastolic function, and glomerular architecture of the kidney. However, elamipretide is a short tetrameric peptide that is not orally bioavailable, limiting its routes of administration. This study tested whether twice weekly intermittent injections of elamipretide could recapitulate the same functional improvements as continuous long-term infusion. We found that intermittent treatment with elamipretide for 8 months preserved exercise tolerance and left ventricular mass in mice with modest protection of diastolic function and skeletal muscle force production but did not affect kidney function as previously reported using continuous treatment.

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Abbreviations

GAS:

Gastrocnemius

TA:

Tibialis anterior

ELAM:

Elamipretide

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Acknowledgements

The authors would like to thank Rudy Stuppard for technical assistance with all aspects of this study. Elamipretide was provided by Stealth Biotherapeutics, Inc.

Funding

This work was supported by the National Institute of Health grants P01 AG001751 and T32 AG000057, the University of Washington Nathan Shock Center P30 AA013280, and the University of Washington Center for Translational Muscle Research P30 AR074990.

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Authors and Affiliations

  1. Department of Radiology, University of Washington, Seattle, WA, 98109, USA

    Matthew D. Campbell, Ashton T. Samuelson & David J. Marcinek

  2. Oregon Health Sciences Surgical Residency Program, Portland, OR, 97239, USA

    Ashton T. Samuelson

  3. Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA

    Ying Ann Chiao & Peter S. Rabinovitch

  4. Aging & Metabolism Research Program MS21, Oklahoma Medical Research Foundation, Oklahoma City, OK, 73104, USA

    Ying Ann Chiao

  5. Department of Laboratory Medicine, University of Washington, Seattle, WA, 98109, USA

    Mariya T. Sweetwyne

  6. Department of Comparative Medicine, University of Washington, Seattle, WA, 98109, USA

    Warren C. Ladiges

  7. South Lake Union Campus, 850 Republican St., Brotman D142, Box 358050, Seattle, WA, 98109, USA

    David J. Marcinek

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  1. Matthew D. Campbell
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  2. Ashton T. Samuelson
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  3. Ying Ann Chiao
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  4. Mariya T. Sweetwyne
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  6. Peter S. Rabinovitch
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  7. David J. Marcinek
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Correspondence to David J. Marcinek.

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Campbell, M.D., Samuelson, A.T., Chiao, Y.A. et al. Intermittent treatment with elamipretide preserves exercise tolerance in aged female mice. GeroScience 45, 2245–2255 (2023). https://doi.org/10.1007/s11357-023-00754-0

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  • DOI: https://doi.org/10.1007/s11357-023-00754-0

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