A shift in energy metabolism anticipates the onset of sarcopenia in rhesus monkeys
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Summary: Age‐associated skeletal muscle mass loss curtails quality of life and may contribute to defects in metabolic homeostasis in older persons. The onset of sarcopenia occurs in middle age in rhesus macaques although the trigger has yet to be identified. Here, we show that a shift in metabolism occurs in advance of the onset of sarcopenia in rhesus vastus lateralis. Multiphoton laser‐scanning microscopy detects a shift in the kinetics of photon emission from autofluorescent metabolic cofactors NADH and FAD. Lifetime of both fluorophores is shortened at mid‐age, and this is observed in both free and bound constituent pools. Levels of FAD and free NADH are increased and the NAD/NADH redox ratio is lower. Concomitant with this, expression of fiber‐type myosin isoforms is altered resulting in a shift in fiber‐type distribution, activity of cytochrome c oxidase involved in mitochondrial oxidative phosphorylation is significantly lower, and the subcellular organization of mitochondria in oxidative fibers is compromised. A regulatory switch involving the transcriptional coactivator PGC‐1α directs metabolic fuel utilization and governs the expression of structural proteins. Age did not significantly impact total levels of PGC‐1α; however, its subcellular localization was disrupted, suggesting that PGC‐1α activities may be compromised. Consistent with this, intracellular lipid storage is altered and there is shift to larger lipid droplet size that likely reflects a decline in lipid turnover or a loss in efficiency of lipid metabolism. We suggest that changes in energy metabolism contribute directly to skeletal muscle aging in rhesus monkeys.
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In old age, a metabolic shift resulting in reduced lipid turnover has been reported to precede the onset of sarcopenia.
“in old age, a metabolic shift resulting in reduced lipid turnover has been reported to precede the onset of sarcopenia [95].”
From Targeting Intramyocellular Lipids to Improve Aging Muscle Function (2025) · cites this paper as [95]
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Self-citationTargeting Intramyocellular Lipids to Improve Aging Muscle Function
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“…flexibility is appropriate shifting between lipid and CHO metabolism and data indicate that sarcopenic older adults manifest reduced lipid oxidation (though not lipolysis) during post-prandial resting metabolism and aerobic exercise [80] and has been found to precede onset of sarcopenia [95].”
- Authors
- Pugh, T. D., Conklin, M. W., Evans, T. D., Polewski, M. A., Barbian, H. J., Pass, R., Anderson, B. D., Colman, R. J., Eliceiri, K. W., Keely, P. J., Weindruch, R., Beasley, T. M., & Anderson, R. M.
- Affiliations
- University of Wisconsin–Madison (US)
- University of Alabama at Birmingham (US)
- Corresponding author
- Anderson, Rozalyn M.
- ORCID
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2013-05-27
- Volume
- 12
- Issue
- 4
- Pages
- 672-681
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- PMC
- PMC3714309
- OpenAlex
- W2094625212
- Cited by
- 81
- References
- 49
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 9 · 2023: 5 · 2022: 7 · 2021: 6 · 2020: 5 · 2019: 5 · 2018: 11 · 2017: 6 · 2016: 8 · 2015: 5 · 2014: 5 · 2013: 1
- FWCI
- 2.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Aging Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UL1TR000427, P51OD011106)
- National Institute on Aging (R01AG037000, R01AG040178, P01AG011915)
- National Cancer Institute (R01CA13659, P30CA014520)
- National Institute of Biomedical Imaging and Bioengineering (R21EB008811)
- National Center for Research Resources (UL1RR025011)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- sarcopenia, skeletal muscle aging, rhesus monkeys, energy metabolism, NADH autofluorescence, FAD autofluorescence, myosin isoforms, fiber type shift, cytochrome c oxidase, mitochondrial oxidative phosphorylation, PGC-1α, lipid droplets, lipid metabolism, vastus lateralis
- MeSH terms
- Aging, Animals, Electron Transport Complex IV, Energy Metabolism, Female, Macaca mulatta, Male, Mitochondria, Oxidation-Reduction, Oxidative Phosphorylation, Transcription Factors, Age of Onset, Muscle Fibers, Skeletal, Caloric Restriction, Lipid Metabolism, Sarcopenia
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