Diminished overload-induced hypertrophy in aged fast-twitch skeletal muscle is associated with AMPK hyperphosphorylation
Abstract
Skeletal muscle mass declines with age, as does the potential for overload-induced fast-twitch skeletal muscle hypertrophy. Because 5′-AMP-activated protein kinase (AMPK) activity is thought to inhibit skeletal muscle protein synthesis and may therefore modulate muscle mass and hypertrophy, the purpose of this investigation was to examine AMPK phosphorylation status (a marker of AMPK activity) and its potential association with the attenuated overload-induced hypertrophy observed in aged skeletal muscle. One-week overload of fast-twitch plantaris and slow-twitch soleus muscles was achieved in young adult (8 mo; n = 7) and old (30 mo; n = 7) Fischer 344 × Brown Norway male rats via unilateral gastrocnemius ablation. Significant ( P ≤ 0.05) age-related atrophy (as measured by total protein content) was noted in plantaris and soleus control (sham-operated) muscles. In fast-twitch plantaris muscles, percent hypertrophy with overload was significantly attenuated with age, whereas AMPK phosphorylation status as determined by Western blotting [phospho-AMPK (Thr172)/total AMPK] was significantly elevated with age (regardless of loading status). There was also a main effect of loading on AMPK phosphorylation status in plantaris muscles (overload > control). Moreover, a strong and significant negative correlation ( r = −0.82) was observed between AMPK phosphorylation status and percent hypertrophy in the overloaded plantaris muscles of all animals. In contrast to the plantaris, overload-induced hypertrophy of the slow-twitch soleus muscle was similar between ages, and AMPK phosphorylation in this muscle was also unaffected by age or overload. These data support the possibility that an age-related elevation in AMPK phosphorylation may partly contribute to the attenuated hypertrophic response observed with age in overloaded fast-twitch plantaris muscle.
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Impaired muscle growth was seen in rats where AMPK activity was higher, supporting the hypothesis that AMPK mediated the concurrent training effect.
“Thomson and Gordon were the first to show that impaired muscle growth was seen in rats where AMPK activity was higher, supporting the hypothesis that AMPK mediated the concurrent training effect [46].”
From Using Molecular Biology to Maximize Concurrent Training (2014) · cites this paper as [46]
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“Regardless of the mechanism, putting together the effect of metabolic stress/AMPK activation on mTOR and the fact that metabolic stress and AMPK activity were increased during endurance exercise, exercise physiologists began to ask the question ‘‘can AMPK limit muscle hypertrophy?’’ Thomson and Gordon were the first t…”
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- Authors
- Thomson, D. M., & Gordon, S. E.
- Affiliations
- East Carolina University (US)
- ORCID
- Thomson, David M.
- Venue
- Journal of Applied Physiology
- Publisher
- American Physiological Society
- Published
- 2005-02
- Volume
- 98
- Issue
- 2
- Pages
- 557-564
- ISSN
- 0161-7567 (ISSN-L)
- 8750-7587
- 1522-1601
- OpenAlex
- W2149490207
- Cited by
- 131
- References
- 53
- Citations by year
- 2026: 3 · 2025: 3 · 2023: 7 · 2022: 3 · 2021: 4 · 2020: 2 · 2019: 11 · 2018: 8 · 2017: 3 · 2016: 7 · 2015: 8 · 2014: 7 · 2013: 4 · 2012: 9
- FWCI
- 2.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Applied Physiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Keywords
- AMPK phosphorylation, skeletal muscle hypertrophy, aging, fast-twitch muscle, slow-twitch muscle, muscle overload, muscle atrophy, plantaris muscle, soleus muscle, skeletal muscle protein synthesis, age-related muscle loss
- MeSH terms
- Aging, Animals, Male, Multienzyme Complexes, Muscular Atrophy, Organ Size, Rats, Inbred F344, Cumulative Trauma Disorders, Severity of Illness Index, Protein Serine-Threonine Kinases, Muscle, Skeletal, Muscle Fibers, Fast-Twitch, Rats, AMP-Activated Protein Kinases
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