J Appl Physiol. 2008 Mar 6 Skeletal muscle protein anabolic response to resistance exercise and essential amino acids is delayed with aging. Drummond MJ, Dreyer HC, Pennings B, Fry CS, Dhanani S, Dillon EL, Sheffield-Moore M, Volpi E, Rasmussen BB. Skeletal muscle loss during aging leads to an increased risk of falls, fractures and eventually loss of independence. Resistance exercise is a useful intervention to prevent sarcopenia, however, the muscle protein synthesis (MPS) response to resistance exercise is less in elderly when compared with young subjects. On the other hand, essential amino acids (EAA) increase MPS equally in both young and old subjects when sufficient EAA is ingested. We hypothesized that EAA ingestion following a bout of resistance exercise would stimulate anabolic signaling and MPS similarly between young and old men. Each subject ingested 20g of EAA 1hr following leg resistance exercise. Muscle biopsies were obtained before, 1, 3, and 6hr post-exercise to measure the rate of MPS and signaling pathways which regulate translation initiation. MPS increased early in young (1-3hr post-exercise) and later in old (3-6hr post-exercise). At 1hr post-exercise, ERK1/2 and MNK1 phosphorylation increased and eIF2alpha phosphorylation decreased only in the young. mTOR signaling (mTOR, S6K1, 4E-BP1, eEF2) was similar between groups at all time points but MNK1 phosphorylation was lower at 3hr and AMPKalpha phosphorylation was higher in old 1-3hr post-exercise. We conclude that the acute MPS response after resistance exercise and EAA ingestion is similar between young and old men, however, the response is delayed with aging. Unresponsive ERK1/2 signaling and AMPK activation in old muscle may be playing a role in the delayed activation of muscle protein synthesis. Notwithstanding, the combination of resistance exercise and EAA ingestion should be a useful strategy to combat sarcopenia. Key words: Resistance Exercise, Aging, Protein Synthesis, Cell Signaling.