The response of muscle protein anabolism to combined hyperaminoacidemia and glucose-induced hyperinsulinemia is impaired in the elderly

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.

Fig. 1

Study design. See text for details.

Fig. 2

Phenylalanine and glucose enrichments. Time course of phenylalanine and glucose enrichments in the femoral artery and vein in healthy young (30 ± 3 yr) and elderly (72 ± 1 yr) subjects in the basal state (270–300 min) and during the intake of an amino acid-glucose mixture (450–480 min). The enrichments were given at steady state during both sampling periods. Values are the mean ± SE.

Fig. 3

Muscle protein synthesis. The FSR of muscle proteins in healthy young (30 ± 3 yr) and elderly (72 ± 1 yr) subjects in the basal state and during the intake of an amino acid-glucose mixture. Values are the mean ± SE. *, P < 0.01 vs. basal; §, P < 0.05 vs. young.

Fig. 4

Comparison of the effects of the amino acid-glucose supplement (present study) vs. the same amount of amino acids alone (14) on muscle protein anabolism in young and elderly subjects. Muscle protein anabolism was measured as phenylalanine net balance across the leg in two comparable groups of young (present study: n = 5, 30 ± 3 yr; from Ref. : n = 7, 30 ± 2 yr) and elderly subjects (present study: n = 5, 72 ± 1 yr; from Ref. , n = 8, 71 ± 2 yr) in the basal state, and during the oral intake of the same amount of a mixed amino acid supplement with or without glucose. Phenylalanine net balance across the leg increased significantly during oral supplementation in all groups. However, compared with amino acids alone the addition of glucose to the supplement induced a significantly higher response in the young, whereas it did not add any benefit in the elderly. Values are the mean ± SE. *, P < 0.01 vs. basal; §, P < 0.05 vs. others.