Age-related anabolic resistance after endurance-type exercise in healthy humans

Abstract

Age-related skeletal muscle loss is thought to stem from suboptimal nutrition and resistance to anabolic stimuli. Impaired microcirculatory (nutritive) blood flow may contribute to anabolic resistance by reducing delivery of amino acids to skeletal muscle. In this study, we employed contrast-enhanced ultrasound, microdialysis sampling of skeletal muscle interstitium, and stable isotope methodology, to assess hemodynamic and metabolic responses of older individuals to endurance type (walking) exercise during controlled amino acid provision. We hypothesized that older individuals would exhibit reduced microcirculatory blood flow, interstitial amino acid concentrations, and amino acid transport when compared with younger controls. We report for the first time that aging induces anabolic resistance following endurance exercise, manifested as reduced (by ∼40%) efficiency of muscle protein synthesis. Despite lower (by ∼40-45%) microcirculatory flow in the older than in the younger participants, circulating and interstitial amino acid concentrations and phenylalanine transport into skeletal muscle were all equal or higher in older individuals than in the young, comprehensively refuting our hypothesis that amino acid availability limits postexercise anabolism in older individuals. Our data point to alternative mediators of age-related anabolic resistance and importantly suggest correction of these impairments may reduce requirements for, and increase the efficacy of, dietary protein in older individuals.

Figure 1.

Study timeline. ICG, indocyanine green sampling; EX, exercise at ∼40% VO₂peak; POST-EX, postexercise; CEU, contrast-enhanced ultrasound.

Figure 2.

Total leg blood flow and skeletal muscle nutritive flow. A) Leg blood flow did not differ between young and older groups. ^#P < 0.0001 for time effect. B) Microvascular blood flow was different between young and older groups and between rest and 60-post groups. *P = 0.03 for young vs. older groups; ^#P = 0.006 for rest vs. 60-post groups. C) Microvascular blood volume increased postexercise but did not differ between young and older individuals. ^#P = 0.0006. D) Microvascular flow velocity did not differ between age groups or times. E) Interstitial ethanol exchange was marginally different between age groups (P=0.06), with a significant effect of time. ^#P = 0.0006 for time effect.

Figure 3.

Amino acid availability. A–F) Both arterial (A, C, E) and interstitial (B, D, F) concentrations of leucine (A, B), phenylalanine (C, D), and the sum of the essential amino acids (EAA; E, F) increased with time; ^#P < 0.0001. Arterial leucine concentrations (A) and interstitial phenylalanine concentrations were significantly higher in older subjects; *P = 0.04. G, H) Total (endogenous+exogenous; G) and endogenous (H) rates of phenylalanine appearance in the circulation were lower in the older individuals and exhibited a significant effects of time. *P = 0.007 vs. younger group; ^#P<0.0001 (G), ^#P = 0.02 (H) for time effect. See also Results and Supplemental Tables 1 and 2 for other amino acids.

Figure 4.

Skeletal muscle phenylalanine trafficking. A) Intracellular rate of appearance was significantly different between young and older subjects, with a significant effect of time. *P = 0.01 vs. younger group; ^#P = 0.0005 for time effect. B) Outward transport efficiency was different between young and older subjects, with a significant effect of time. *P = 0.05 vs. younger group; ^#P = 0.0001 for time effect. C) Synthetic efficiency was higher in young than in older subjects, with a significant effect of time. *P = 0.05 vs. younger group; ^#P = 0.0001 for time effect.