Aging impairs contraction-induced human skeletal muscle mtorc1 signaling and protein synthesis

Fry, Christopher S; Drummond, Micah J; Glynn, Erin L; Dickinson, Jared M; Gundermann, David M; Timmerman, Kyle L; Walker, Dillon K; Dhanani, Shaheen; Volpi, Elena; Rasmussen, Blake B

doi:10.1186/2044-5040-1-11

Cited by 351Muscle metabolism and nutritionMuscle Physiology and DisordersNutrition and Health in Aging

Aging impairs contraction-induced human skeletal muscle mtorc1 signaling and protein synthesis

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Fry, Christopher S, Drummond, Micah J, Glynn, Erin L, Dickinson, Jared M, Gundermann, David M, Timmerman, Kyle L, Walker, Dillon K, Dhanani, Shaheen +2 more·2011·Skeletal Muscle

DOI 10.1186/2044-5040-1-11PMC PMC3156634

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Abstract

BACKGROUND: Sarcopenia, the loss of skeletal muscle mass during aging, increases the risk for falls and dependency. Resistance exercise (RE) training is an effective treatment to improve muscle mass and strength in older adults, but aging is associated with a smaller amount of training-induced hypertrophy. This may be due in part to an inability to stimulate muscle-protein synthesis (MPS) after an acute bout of RE. We hypothesized that older adults would have impaired mammalian target of rapamycin complex (mTORC)1 signaling and MPS response compared with young adults after acute RE. METHODS: We measured intracellular signaling and MPS in 16 older (mean 70 ± 2 years) and 16 younger (27 ± 2 years) subjects. Muscle biopsies were sampled at baseline and at 3, 6 and 24 hr after exercise. Phosphorylation of regulatory signaling proteins and MPS were determined on successive muscle biopsies by immunoblotting and stable isotopic tracer techniques, respectively. RESULTS: Increased phosphorylation was seen only in the younger group (P< 0.05) for several key signaling proteins after exercise, including mammalian target of rapamycin (mTOR), ribosomal S6 kinase (S6K)1, eukaryotic initiation factor 4E-binding protein (4E-BP)1 and extracellular signal-regulated kinase (ERK)1/2, with no changes seen in the older group (P >0.05). After exercise, MPS increased from baseline only in the younger group (P< 0.05), with MPS being significantly greater than that in the older group (P <0.05). CONCLUSIONS: We conclude that aging impairs contraction-induced human skeletal muscle mTORC1 signaling and protein synthesis. These age-related differences may contribute to the blunted hypertrophic response seen after resistance-exercise training in older adults, and highlight the mTORC1 pathway as a key therapeutic target to prevent sarcopenia.

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With increasing age, skeletal muscle becomes less responsive to anabolic stimuli such as resistance exercise and protein feeding.
“With increasing age, skeletal muscle becomes less responsive to anabolic stimuli, such as resistance exercise and protein feeding.”
From Potential Roles of n-3 PUFAs during Skeletal Muscle Growth and Regeneration (2018) · cites this paper as [5]
Reduced sensitivity to anabolic stimuli, termed anabolic resistance, is implicated in the etiology of sarcopenia.
“It is thought that this reduced sensitivity to anabolic stimuli, termed ”anabolic resistance”, is implicated in the etiology of sarcopenia, which is the gradual loss of muscle mass with age [2,3,4,5,6,7].”
From Potential Roles of n-3 PUFAs during Skeletal Muscle Growth and Regeneration (2018) · cites this paper as [5]

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Authors: Fry, C. S., Drummond, M. J., Glynn, E. L., Dickinson, J. M., Gundermann, D. M., Timmerman, K. L., Walker, D. K., Dhanani, S., Volpi, E., & Rasmussen, B. B.
Affiliations: The University of Texas Medical Branch at Galveston (US)
Corresponding author: Rasmussen, Blake B
ORCID: Fry, Christopher S
Drummond, Micah J
Glynn, Erin L
Dickinson, Jared M
Gundermann, David M
Timmerman, Kyle L
Volpi, Elena
Rasmussen, Blake B
Venue: Skeletal Muscle
Publisher: Springer Science and Business Media LLC
Published: 2011-03-02
Volume: 1
Issue: 1
Pages: 11-11
ISSN: 2044-5040 (ISSN-L)
DOI: 10.1186/2044-5040-1-11
PMC: PMC3156634
OpenAlex: W2145390098
Cited by: 351
References: 55
Citations by year: 2026: 17 · 2025: 14 · 2024: 9 · 2023: 20 · 2022: 24 · 2021: 33 · 2020: 23 · 2019: 19 · 2018: 20 · 2017: 25 · 2016: 38 · 2015: 34 · 2014: 26 · 2013: 18 · 2012: 23
FWCI: 11.50
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
Locations: Skeletal Muscle (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: National Institutes of Health (NIH T32, UL1TR000071, AG024832)
National Institute on Aging (AG024832, P30AG024832)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR049877, AR049877)
National Center for Research Resources (UL1RR029876)
National Center for Advancing Translational Sciences
Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD007539)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
Keywords: sarcopenia, aging, mTORC1 signaling, muscle protein synthesis, resistance training, skeletal muscle hypertrophy, older adults, S6K1, 4E-BP1, ERK1/2, protein phosphorylation

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Aging impairs contraction-induced human skeletal muscle mtorc1 signaling and protein synthesis

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