Cited by 204Muscle metabolism and nutritionNutrition and Health in AgingMuscle Physiology and Disorders

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Blunting of insulin inhibition of proteolysis in legs of older subjects may contribute to age-related sarcopenia

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Wilkes, Emilie A, Selby, Anna L, Atherton, Philip J, Patel, Rekha, Rankin, Debbie, Smith, Ken, Rennie, Michael J·2009·The American Journal of Clinical Nutrition

DOI 10.3945/ajcn.2009.27543

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Abstract

Background Reduced postprandial muscle proteolysis is mainly due to increased insulin availability. Whether rates of proteolysis in response to low physiologic doses of insulin are affected by aging is unknown. Objectives We tested the hypothesis that suppression of leg protein breakdown (LPB) by insulin is blunted in older subjects, together with blunted activation of Akt-protein kinase B (PKB). Design Groups of 8 young [mean (+/-SD) age: 24.5 +/- 1.8 y] and older (65.0 +/- 1.3 y) participants were studied during euglycemic (5 mmol/L), isoaminoacidemic (blood leucine approximately 120 micromol/L) clamp procedures at plasma insulin concentrations of approximately 5 and approximately 15 microIU/mL for 1.5 h. Leg amino acid balance, whole-leg protein turnover (as dilution of amino acid tracers), and muscle protein synthesis were measured with D(5)-phenylalanine and [1,2-(13)C(2)]leucine. The kinase activity of muscle Akt-PKB and the extent of phosphorylation of signaling proteins associated with the mTOR (mammalian target of rapamycin) pathway were measured before and after the clamp procedures. Results Basal LPB rates were not different between groups (66 +/- 11 compared with 51 +/- 10 nmol leucine x 100 mL leg(-1) x min(-1) and 30 +/- 5 compared with 24 +/- 4 nmol phenylalanine x 100 mL leg(-1) x min(-1) in young and older groups, respectively). However, although insulin at approximately 15 microIU/mL lowered LPB by 47% in the young subjects (P < 0.05) and abolished the negative leg amino acid balance, this caused only a 12% fall (P > 0.05) in the older group. Akt-PKB activity mirrored decreases in LPB. No differences were seen in muscle protein synthesis or associated anabolic signaling phosphoproteins. Conclusions At moderate availability, the effect of insulin on LPB is diminished in older human beings, and this effect may be mediated through blunted Akt-PKB activation.

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Authors: Wilkes, E. A., Selby, A. L., Atherton, P. J., Patel, R., Rankin, D., Smith, K., & Rennie, M. J.
Affiliations: University of Nottingham (GB)
Corresponding author: Rennie, Michael J
ORCID: Wilkes, Emilie A
Selby, Anna L
Atherton, Philip J
Patel, Rekha
Rankin, Debbie
Rennie, Michael J
Venue: The American Journal of Clinical Nutrition
Publisher: Elsevier BV
Published: 2009-11
Volume: 90
Issue: 5
Pages: 1343-1350
ISSN: 0002-9165 (ISSN-L)
DOI: 10.3945/ajcn.2009.27543
OpenAlex: W2118035665
Cited by: 204
References: 47
Citations by year: 2026: 6 · 2025: 5 · 2024: 4 · 2023: 11 · 2022: 10 · 2021: 14 · 2020: 17 · 2019: 12 · 2018: 12 · 2017: 8 · 2016: 17 · 2015: 11 · 2014: 13 · 2013: 18 · 2012: 18
FWCI: 6.83
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 4862 d)
Locations: American Journal of Clinical Nutrition (publishedVersion)
PubMed (publishedVersion)
Funders: Biotechnology and Biological Sciences Research Council (BB/X5106971, BB/C516779/1)
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: insulin resistance, muscle protein degradation, aging, sarcopenia, Akt/protein kinase B, mTOR signaling, muscle protein synthesis, older adults
MeSH terms: Adult, Aged, Aging, Amino Acids, Female, Humans, Insulin, Leg, Leucine, Male, Muscle Proteins, Muscular Diseases, Proteins, Glucose Clamp Technique, Proto-Oncogene Proteins c-akt

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Blunting of insulin inhibition of proteolysis in legs of older subjects may contribute to age-related sarcopenia

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