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Skeletal muscle bioenergetics in aging and heart failure

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Abstract

Changes in mitochondrial capacity and quality play a critical role in skeletal and cardiac muscle dysfunction. In vivo measurements of mitochondrial capacity provide a clear link between physical activity and mitochondrial function in aging and heart failure, although the cause and effect relationship remains unclear. Age-related decline in mitochondrial quality leads to mitochondrial defects that affect redox, calcium, and energy-sensitive signaling by altering the cellular environment that can result in skeletal muscle dysfunction independent of reduced mitochondrial capacity. This reduced mitochondrial quality with age is also likely to sensitize skeletal muscle mitochondria to elevated angiotensin or beta-adrenergic signaling associated with heart failure. This synergy between aging and heart failure could further disrupt cell energy and redox homeostasis and contribute to exercise intolerance in this patient population. Therefore, the interaction between aging and heart failure, particularly with respect to mitochondrial dysfunction, should be a consideration when developing strategies to improve quality of life in heart failure patients. Given the central role of the mitochondria in skeletal and cardiac muscle dysfunction, mitochondrial quality may provide a common link for targeted interventions in these populations.

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Acknowledgments

This publication was supported by awards from the National Institute on Aging of the National Institutes of Health AG001751 and AG000057 and a Breakthrough in Gerontology Award from the American Federation for Aging Research.

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Authors and Affiliations

  1. Department of Radiology, University of Washington, Box 358050, Seattle, WA, 98109, USA

    Sophia Z. Liu & David J. Marcinek

  2. Department of Pathology, University of Washington, Seattle, WA, 98109, USA

    David J. Marcinek

  3. Department of Bioengineering, University of Washington, Seattle, WA, 98109, USA

    David J. Marcinek

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  1. Sophia Z. Liu
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  2. David J. Marcinek
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Correspondence to David J. Marcinek.

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David Marcinek serves as a paid consultant to Stealth BioTherapeutics. Stealth is developing the compound elamipretide (SS-31) for clinical use. Sophia Liu has no conflict of interest to report.

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Liu, S.Z., Marcinek, D.J. Skeletal muscle bioenergetics in aging and heart failure. Heart Fail Rev 22, 167–178 (2017). https://doi.org/10.1007/s10741-016-9586-z

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