PGC‐1α affects aging‐related changes in muscle and motor function by modulating specific exercise‐mediated changes in old mice
Open accessAbstract
The age-related impairment in muscle function results in a drastic decline in motor coordination and mobility in elderly individuals. Regular physical activity is the only efficient intervention to prevent and treat this age-associated degeneration. However, the mechanisms that underlie the therapeutic effect of exercise in this context remain unclear. We assessed whether endurance exercise training in old age is sufficient to affect muscle and motor function. Moreover, as muscle peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is a key regulatory hub in endurance exercise adaptation with decreased expression in old muscle, we studied the involvement of PGC-1α in the therapeutic effect of exercise in aging. Intriguingly, PGC-1α muscle-specific knockout and overexpression, respectively, precipitated and alleviated specific aspects of aging-related deterioration of muscle function in old mice, while other muscle dysfunctions remained unchanged upon PGC-1α modulation. Surprisingly, we discovered that muscle PGC-1α was not only involved in improving muscle endurance and mitochondrial remodeling, but also phenocopied endurance exercise training in advanced age by contributing to maintaining balance and motor coordination in old animals. Our data therefore suggest that the benefits of exercise, even when performed at old age, extend beyond skeletal muscle and are at least in part mediated by PGC-1α.
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PGC-1α mediates the beneficial effects of exercise training on aging-related mitochondrial remodeling and muscle functional deterioration in old mice.
“PGC-1α has also been reported to mediate the beneficial effects of exercise training on aging-related mitochondrial remodeling and muscle functional deterioration in old mice (78).”
From From mitochondria to sarcopenia: role of 17β-estradiol and testosterone (2023) · cites this paper as [78]
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Mouse Fitness as Determined Through Treadmill Running and Walking
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- Authors
- Gill, J. F., Santos, G., Schnyder, S., & Handschin, C.
- Affiliations
- University of Basel (CH)
- Corresponding author
- Handschin, Christoph
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2017-10-25
- Volume
- 17
- Issue
- 1
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- PMC
- PMC5770876
- OpenAlex
- W2765916581
- Cited by
- 72
- References
- 45
- Citations by year
- 2026: 10 · 2025: 5 · 2024: 6 · 2023: 12 · 2022: 6 · 2021: 6 · 2020: 13 · 2019: 9 · 2018: 3 · 2017: 2
- FWCI
- 3.02
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Aging Cell (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- edoc (University of Basel) (acceptedVersion)
- edoc (University of Basel)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- H2020 European Research Council (616830‐MUSCLE_NET)
- Novartis Stiftung für Medizinisch-Biologische Forschung
- Universität Basel
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- PGC-1α, skeletal muscle aging, endurance training, motor coordination, balance, mitochondrial remodeling, muscular endurance
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Aging, Animals, Mitochondria, Mitochondria, Muscle, Physical Conditioning, Animal, Transcription Factors, Muscle, Skeletal, Mice
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