Aging impairs contraction-induced human skeletal muscle mTORC1 signaling and protein synthesis

We measured intracellular signaling and MPS in 16 older (mean 70 ± 2 years) and 16 younger (27 ± 2 years) subjects. Muscle biopsies were sampled at baseline and at 3, 6 and 24 hr after exercise. Phosphorylation of regulatory signaling proteins and MPS were determined on successive muscle biopsies by immunoblotting and stable isotopic tracer techniques, respectively.Increased phosphorylation was seen only in the younger group (P< 0.05) for several key signaling proteins after exercise, including mammalian target of rapamycin (mTOR), ribosomal S6 kinase (S6K)1, eukaryotic initiation factor 4E-binding protein (4E-BP)1 and extracellular signal-regulated kinase (ERK)1/2, with no changes seen in the older group (P >0.05). After exercise, MPS increased from baseline only in the younger group (P< 0.05), with MPS being significantly greater than that in the older group (P <0.05).We conclude that aging impairs contraction-induced human skeletal muscle mTORC1 signaling and protein synthesis. These age-related differences may contribute to the blunted hypertrophic response seen after resistance-exercise training in older adults, and highlight the mTORC1 pathway as a key therapeutic target to prevent sarcopenia.Maintenance of skeletal muscle mass is largely dependent on the dynamic relationship of muscle-protein balance, which is the relationship between protein synthesis and protein breakdown. A net negative protein balance is indicative of muscle atrophy, whereas a net positive balance yields an accrual of muscle proteins. In numerous disease states, such as HIV/AIDS, cancer, sepsis and renal failure, the rate of muscle-protein breakdown exceeds that of synthesis, and catabolism of muscle occurs, resulting in measurable atrophy [1-3]. Loss of muscle mass also occurs with the aging process (sarcopenia), although the atrophy of aging is not as severe as that seen in various disease states, as it arises over the span of several decades. Resting rates of muscle protein turnover ha