Anabolic signaling deficits underlie amino acid resistance of wasting, aging muscle

SPECIFIC AIMSHealthy aging is associated with wasting of skeletal muscle of unknown cause. We hypothesized that, for lack of good evidence of derangements of muscle protein turnover in the basal, post-absorptive state, the deficit in the muscle maintenance must lie elsewhere, possibly in a diminished response to amino acids, the most anabolically potent of nutrients. We aimed to test this by measuring the responses to mixed oral essential amino acids (EAA) of 1) skeletal muscle protein synthesis (MPS) and 2) components of anabolic signaling pathways in healthy young and elderly men.PRINCIPAL FINDINGSWe studied 44 young and elderly men (means±sd, respectively: age, 28±1, 70±1 y; body mass index, (BMI), 24±3, 26±4 kg.m–2; skeletal muscle mass, 33±4, 28±4 kg, P<0.01). We measured the fractional synthetic rates (FSR) of protein in their m. vastus lateralis as the rate of incorporation of [13C] leucine from a primed, constant infusion of [1-13C]α-ketoisocaproic acid, over 3 h after they drank solutions of 0–40...