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The Response of Muscle Protein Anabolism to Combined Hyperaminoacidemia and Glucose-Induced Hyperinsulinemia Is Impaired in the Elderly1
Open accessAbstract
Muscle mass declines with aging. Amino acids alone stimulate muscle protein synthesis in the elderly. However, mixed nutritional supplementation failed to improve muscle mass. We hypothesized that the failure of nutritional supplements is due to altered responsiveness of muscle protein anabolism to increased amino acid availability associated with endogenous hyperinsulinemia. We measured muscle protein synthesis and breakdown, and amino acid transport in healthy young (30 +/- 3 yr) and elderly (72 +/- 1 yr) volunteers in the basal postabsorptive state and during the administration of an amino acid-glucose mixture, using L-[ring-(2)H(5)]phenylalanine infusion, femoral artery and vein catheterization, and muscle biopsies. Basal muscle amino acid turnover was similar in young and elderly subjects. The mixture increased phenylalanine leg delivery and transport into the muscle in both groups. Phenylalanine net balance increased in both groups (young, -27 +/- 8 to 64 +/- 17; elderly, -16 +/- 4 to 29 +/- 7 nmol/(min.100 mL); P: < 0.0001, basal vs. mixture), but the increase was significantly blunted in the elderly (P: = 0.030 vs. young). Muscle protein synthesis increased in the young, but remained unchanged in the elderly [young, 61 +/- 17 to 133 +/- 30 (P: = 0. 005); elderly, 62 +/- 9 to 70 +/- 14 nmol/(min.100 mL) (P: = NS)]. In both groups, protein breakdown decreased (P: = 0.012) and leg glucose uptake increased (P: = 0.0258) with the mixture. We conclude that the response of muscle protein anabolism to hyperaminoacidemia with endogenous hyperinsulinemia is impaired in healthy elderly due to the unresponsiveness of protein synthesis.
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“In the fed state, however, most researchers now agree that there is an impairment of the muscle protein anabolic response to meal intake in older adults, 46,49,50 although some studies found no difference between older and younger adults, especially when high amounts of amino acids or proteins were administered.”
From Evidence-Based Recommendations for Optimal Dietary Protein Intake in Older People: A Position Paper From the PROT-AGE Study Group (2013) · cites this paper as [49]
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“Consistent with the anabolic resistance hypothesis, muscle protein breakdown did not change in either age-group, however, muscle protein synthesis increased only in the young.”
From Protecting muscle mass and function in older adults during bed rest (2010) · cites this paper as [18]
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Citations
Cites
Exercise training and nutritional supplementation for physical frailty in very elderly people
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“This may reflect a general response of insulin resistance, because previous studies have reported a similar alteration in the response of blood flow to insulin in type 2 diabetes patients (40, 41).”
ResultExogenous amino acids stimulate net muscle protein synthesis in the elderly.
Volpi, E., Ferrando, A. A., Yeckel, C. W., Tipton, K. D., & Wolfe, R. R. (1998) · Journal of Clinical Investigation · doi:10.1172/jci939 · Cited by 390
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Bauer, J., Biolo, G., Cederholm, T., Cesari, M., Cruz-Jentoft, A. J., Morley, J. E., Phillips, S., Sieber, C., Stehle, P., Teta, D., et al. (2013) · Journal of the American Medical Directors Association · doi:10.1016/j.jamda.2013.05.021 · Cited by 2,553
Self-citationSarcopenic obesity in older adults: aetiology, epidemiology and treatment strategies
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Anabolic signaling deficits underlie amino acid resistance of wasting, aging muscle
Cuthbertson, D., Smith, K., Babraj, J., Leese, G., Waddell, T., Atherton, P., Wackerhage, H., Taylor, P. M., & Rennie, M. J. (2005) · The FASEB Journal · doi:10.1096/fj.04-2640fje · Cited by 1,211
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Self-citation
Metadata
- Authors
- Volpi, E., Mittendorfer, B., Rasmussen, B. B., & Wolfe, R. R.
- Affiliations
- Shriners Hospitals for Children - Galveston (US)
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2000-12
- Volume
- 85
- Issue
- 12
- Pages
- 4481-4490
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC3192447
- OpenAlex
- W2028767281
- Cited by
- 464
- References
- 9
- Citations by year
- 2026: 1 · 2025: 10 · 2024: 9 · 2023: 13 · 2022: 14 · 2021: 16 · 2020: 13 · 2019: 16 · 2018: 16 · 2017: 11 · 2016: 27 · 2015: 34 · 2014: 17 · 2013: 27 · 2012: 36
- FWCI
- 2.57
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- public-domain
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Shriners Hospitals for Children
- National Institutes of Health (RR-00073)
- U.S. Public Health Service
- National Institute on Aging (AG-15780, R01AG015780, P60 AG 17231, P60AG017231, R01AG018311, P30AG024832)
- National Center for Research Resources (M01 RR-00073, M01RR000073)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
- Health Sciences › Medicine › Physiology (medical) › Nutrition and Health in Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- muscle protein anabolism, hyperaminoacidemia, hyperinsulinemia, aging, older adults, muscle protein synthesis, muscle protein degradation, amino acid transport, phenylalanine, glucose uptake, muscle mass, dietary supplementation
- MeSH terms
- Adult, Aged, Aging, Amino Acids, Blood Glucose, Female, Glucose, Hormones, Humans, Hyperinsulinism, Leg, Male, Muscle Proteins, Regional Blood Flow, Muscle, Skeletal
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