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Myostatin Inhibition Enhances the Effects of Exercise on Performance and Metabolic Outcomes in Aged Mice
Abstract
The objective of this study was to examine the effects of short-term exercise training, myostatin inhibition (PF-354), and exercise+PF-354, all relative to a vehicle control, on performance and metabolic measures in 24-month-old mice. At study termination, PF-354-treated mice exhibited significantly greater muscle weights. Performance measures revealed that exercise+PF-354 increased treadmill running time and distance to exhaustion (more than twofold) and increased habitual activity. Measures of strength were not different; however, all treatment groups demonstrated more than 30% reductions in muscle fatigue. Metabolic measures showed that basal metabolic rates were higher in PF-354- and exercise+PF-354-treated mice, and exercise and exercise+PF-354 groups exhibited significantly greater insulin sensitivity. PF-354 was associated with decreased Smad3 phosphorylation and increased peroxisome proliferator-activated receptor gamma coactivator-1alpha expression and, similar to exercise, decreased MuRF-1. The data suggest that the combination of exercise training and myostatin blockade may significantly improve physical function and whole-body metabolism in older individuals.
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“PGC-1α in turn binds to FOXO and inhibits its transcriptional activity (Lebrasseur et al., 2009).”
From Physical Exercise-Induced Myokines and Muscle-Adipose Tissue Crosstalk: A Review of Current Knowledge and the Implications for Health and Metabolic Diseases (2018) · cites this paper as Lebrasseur et al., 2009
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“Importantly, the inhibition of myostatin signaling increases PGC1α and mitochondrial biogenesis 145, while mice deficient for myostatin show an improved metabolic phenotype and a resistance to HFD 146, 147.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [145]
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Metadata
- Authors
- LeBrasseur, N. K., Schelhorn, T. M., Bernardo, B. L., Cosgrove, P. G., Loria, P. M., & Brown, T. A.
- Affiliations
- Pfizer (United States) (US)
- Venue
- The Journals of Gerontology Series A: Biological Sciences and Medical Sciences
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-05-29
- Volume
- 64A
- Issue
- 9
- Pages
- 940-948
- ISSN
- 1079-5006 (ISSN-L)
- 1758-535X
- OpenAlex
- W2165995731
- Cited by
- 180
- References
- 42
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 10 · 2023: 8 · 2022: 12 · 2021: 7 · 2020: 9 · 2019: 9 · 2018: 12 · 2017: 14 · 2016: 17 · 2015: 13 · 2014: 17 · 2013: 16 · 2012: 10
- FWCI
- 4.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journals of Gerontology Series A (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology (medical) › Cardiovascular and exercise physiology
- Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
- Keywords
- myostatin inhibition, exercise training, aging, muscle atrophy, muscle fatigue, endurance performance, insulin sensitivity, basal metabolic rate, Smad3 phosphorylation, PGC-1α, MuRF1, muscle strength, treadmill running
- MeSH terms
- Aging, Animals, Energy Metabolism, Insulin Resistance, Male, Mice, Inbred C57BL, Phosphorylation, Physical Conditioning, Animal, Muscle, Skeletal, Mice, Smad3 Protein, Muscle Strength, Myostatin
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