Skeletal muscle protein anabolic response to resistance exercise and essential amino acids is delayed with aging

Abstract

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 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 3 h and AMP-activated protein kinase-alpha (AMPKalpha) 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.

Cellular mechanisms regulating protein synthesis and skeletal muscle hypertrophy in animals

“…Among the amino acids, changes in leucine levels alone are sufficient to regulate the phosphorylation state and activity of the mTOR pathway (46,69). Several studies in rodents and human have shown that administration/ingestion of essential amino acids (specifically leucine) leads to increased/ enhanced protein synthesis in skeletal muscle primarily through activation of mTOR signaling (5,24,25,32,102). Currently, it is widely accepted that amino acid availability affects mTOR signaling and protein synthesis rate; however, how amino acids regulate the mTOR signaling pathway remains poorly understood.…”

Expression of growth-related genes in young and older human skeletal muscle following an acute stimulation of protein synthesis

“…These volunteers were studied previously and therefore the subject characteristics can be found elsewhere (23). The subjects were not engaged in any regular exercise training at the time of the enrollment, however, they were physically independent and overall healthy.…”

“…This was immediately followed with the ingestion of 20 g of a leucine-enriched essential amino acid mixture. The composition of the essential amino acid mixture was published previously (23). Subsequent muscle biopsies were sampled at 3 and 6 h postexercise.…”

“…This may be due to an inability to fully stimulate muscle protein synthesis following an acute bout of resistance exercise (47). We recently showed that an acute anabolic stimulus (resistance exercise combined with essential amino acid ingestion) can stimulate muscle protein synthesis in older men; however, the response is delayed compared with young men (23). Undoubtedly, more information is needed at the molecular level to determine why skeletal muscle from older individuals is less responsive to an acute anabolic stimulus.…”

“…Muscle protein synthesis is stimulated in both young and old men following an acute anabolic stimulus (resistance exercise followed by essential amino acid ingestion; REϩEAA), however, the response was delayed in the older men (23). The purpose of this study, in an effort to better understand the molecular mechanisms that may explain this delayed response, was to identify select and novel mRNAs associated with mTOR and satellite cell regulation after an acute anabolic stimulus (REϩEAA) in young and older men.…”