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An energetics perspective on geroscience: mitochondrial protonmotive force and aging

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Abstract

Mitochondria are organelles that provide energy to cells through ATP production. Mitochondrial dysfunction has long been postulated to mediate cellular declines that drive biological aging. Many well-characterized hallmarks of aging may involve underlying energetic defects that stem from loss of mitochondrial function with age. Why and how mitochondrial function declines with age is an open question and one that has been difficult to answer. Mitochondria are powered by an electrochemical gradient across the inner mitochondrial membrane known as the protonmotive force (PMF). This gradient decreases with age in several experimental models. However, it is unclear if a diminished PMF is a cause or a consequence of aging. Herein, we briefly review and define mitochondrial function, we summarize how PMF changes with age in several models, and we highlight recent studies that implicate PMF in aging biology. We also identify barriers that must be addressed for the field to progress. Emerging technology permits more precise in vivo study of mitochondria that will allow better understanding of cause and effect in metabolic models of aging. Once cause and effect can be discerned more precisely, energetics approaches to combat aging may be developed to prevent or reverse functional decline.

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Acknowledgements

The authors thank Dr. Gavin Pharoah for critically reviewing the manuscript.

Funding

BJB is supported by the Biological Mechanisms for Healthy Aging (BMHA) Training Grant NIH T32AG066574. MK is the director of the BMHA Training Program and the Nathan Shock Center of Excellence in the Basic Biology of Aging (NIH P30AG013280) at the University of Washington. This work was supported by NIH grant R01NS98329 to MK.

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  1. Department of Laboratory Medicine and Pathology, University of Washington Medical Center, 1959 NE Pacific St, Seattle, WA, 98195, USA

    Brandon J. Berry & Matt Kaeberlein

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BJB wrote and revised the manuscript; MK wrote and revised the manuscript.

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Correspondence to Matt Kaeberlein.

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Berry, B.J., Kaeberlein, M. An energetics perspective on geroscience: mitochondrial protonmotive force and aging. GeroScience 43, 1591–1604 (2021). https://doi.org/10.1007/s11357-021-00365-7

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