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J Appl Physiol 104: 1452-1461, 2008. First published March 6, 2008; doi:10.1152/japplphysiol.00021.2008
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Skeletal muscle protein anabolic response to resistance exercise and essential amino acids is delayed with aging

Micah J. Drummond,1 Hans C. Dreyer,1,2 Bart Pennings,4 Christopher S. Fry,1 Shaheen Dhanani,3,4 Edgar L. Dillon,3,4 Melinda Sheffield-Moore,3,4 Elena Volpi,3,4 and Blake B. Rasmussen1,2,4

1Division of Rehabilitation Sciences, 2Departments of Physical Therapy and 3Internal Medicine, and 4Sealy Center on Aging, University of Texas Medical Branch, Galveston, Texas

Submitted 10 January 2008 ; accepted in final form 5 March 2008

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 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 20 g of EAA 1 h following leg resistance exercise. Muscle biopsies were obtained before and 1, 3, and 6 h after exercise to measure the rate of MPS and signaling pathways that regulate translation initiation. MPS increased early in young (1–3 h postexercise) and later in old (3–6 h postexercise). At 1 h postexercise, ERK1/2 MNK1 phosphorylation increased and eIF2{alpha} 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 3 h and AMP-activated protein kinase-{alpha} (AMPK{alpha}) phosphorylation was higher in old 1–3 h postexercise. 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 MPS. Notwithstanding, the combination of resistance exercise and EAA ingestion should be a useful strategy to combat sarcopenia.

sarcopenia; mammalian target of rapamycin; AMPK; weight lifting


Address for reprint requests and other correspondence: B. B. Rasmussen, Univ. of Texas Medical Branch, Dept. of Physical Therapy, Division of Rehabilitation Sciences, 301 Univ. Blvd., Galveston, TX 77555-1144 (e-mail: blrasmus{at}utmb.edu)




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