Cited by 464Muscle metabolism and nutritionNutrition and Health in AgingMuscle Physiology and Disorders

The Response of Muscle Protein Anabolism to Combined Hyperaminoacidemia and Glucose-Induced Hyperinsulinemia Is Impaired in the Elderly1

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Volpi, Elena, Mittendorfer, Bettina, Rasmussen, Blake B., Wolfe, Robert R.·2000·The Journal of Clinical Endocrinology & Metabolism

Abstract

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, most researchers agree there is an impairment of the muscle protein anabolic response to meal intake in older adults, although some studies found no difference, especially with high amino acid or protein amounts.

    “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.”
  • In young and older adults following a simulated protein/carbohydrate mixed meal, muscle protein breakdown did not change in either age group, but muscle protein synthesis increased only in the young.

    “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.”

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Research works printed but not linked: 4

  1. Wolfe RR, Volpi E. 2000 Insulin and protein metabolism. In: Jefferson LS, Cherrington AD, eds. Handbook of physiology. New York: Oxford University Press; vol 2:733-755.
  2. Wolfe RR. 1992 Appendix A: laboratory methods. In: Radioactive and stable isotope tracers in biomedicine. Principle and practice of kinetic analysis. New York: Wiley-Liss; 417-438.
  3. Wolfe RR. 1992 Calculation of substrate kinetics: single pool model. In: Ra- dioactive and stable isotope tracers in biomedicine. Principle and practice of kinetic analysis. New York: Wiley-Liss; 119 -144.
  4. Welle S, Thornton C, Jozefowicz R, Statt M. 1993 Myofibrillar protein syn- thesis in young and old men. Am J Physiol. 264:E693-E698.

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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
Published
2000-12
Volume
85
Issue
12
Pages
4481-4490
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
OpenAlex
W2028767281
Cited by
464
References
5
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
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
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
  • Health Sciences › Medicine › Physiology › 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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