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

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...

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Published in:The American journal of clinical nutrition 2009-11, Vol.90 (5), p.1343-1350
Main Authors: Wilkes, Emilie A, Selby, Anna L, Atherton, Philip J, Patel, Rekha, Rankin, Debbie, Smith, Ken, Rennie, Michael J
Format: Article
Language:English
Subjects:
Adult
Aged
Aging
Aging - physiology
Amino Acids - blood
Amino Acids - metabolism
Biological and medical sciences
elderly
Feeding. Feeding behavior
Female
Fundamental and applied biological sciences. Psychology
Glucose Clamp Technique
health status
human health
Humans
Insulin
Insulin - blood
Insulin - pharmacology
Kinases
Leg
Legs
Leucine - metabolism
Male
muscle physiology
Muscle Proteins - drug effects
Muscle Proteins - metabolism
muscles
Muscular Diseases - prevention & control
Nutrition
phosphoproteins
Plasma
postprandial state
Proteins
Proteins - metabolism
proteolysis
Proto-Oncogene Proteins c-akt - metabolism
risk factors
senescence
skeletal muscle
Vertebrates: anatomy and physiology, studies on body, several organs or systems
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Summary: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 [almost equal to] 120 μmol/L) clamp procedures at plasma insulin concentrations of [almost equal to]5 and [almost equal to]15 μIU/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 D₅-phenylalanine and [1,2-¹³C₂]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 · 100 mL leg⁻¹ · min⁻¹ and 30 ± 5 compared with 24 ± 4 nmol phenylalanine · 100 mL leg⁻¹ · min⁻¹ in young and older groups, respectively). However, although insulin at [almost equal to]15 μIU/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.
ISSN:0002-9165
1938-3207
DOI:10.3945/ajcn.2009.27543