Michelle M. Farnfield

Activation of mTOR signalling in young and old human skeletal muscle in response to combined resistance exercise and whey protein ingestion

PURPOSE To investigate the impact of whey protein ingestion and resistance exercise training on the phosphorylation of mRNA translational signalling proteins in the skeletal muscle of young and old men. METHODS Sixteen healthy young (aged 18-25 years) and 15 healthy older men (aged 60-75 years) completed 12 weeks of resistance exercise and were randomly assigned to consume a whey protein (WPI) or placebo drink after each session. Muscle biopsies were collected before and 2 h after an acute exercise bout at the beginning and the end of training. RESULTS All subjects significantly increased strength after following strength training. Phosphorylation of mTOR was significantly greater in the WPI groups compared with placebo for both younger and older subjects. Phosphorylation of p70(S6K), eIF4G, and 4EBP1 was greater for older subjects consuming WPI. Phosphorylation of rpS6, eIF4G, and 4EBP1 tended to increase in the younger subjects that had consumed WPI. Post-training, younger subjects demonstrated a similar pattern of mTOR phosphorylation as seen pre-training. In contrast, the initial heightened phosphorylation of mTOR, p70(S6K), rpS6, and eIF4G in older muscle to combined resistance exercise and WPI ingestion became less pronounced after repeated training sessions. CONCLUSIONS In the untrained state, resistance exercise coupled with WPI increases the phosphorylation of proteins involved in mRNA translation compared with exercise alone. Post-training, WPI- and exercise-induced protein phosphorylation was reduced in older men, but not in younger men. Thus, strategies to induce hypertrophy should utilize protein and resistance training concurrently. Further investigations should delineate interventions that will maintain sensitivity to anabolic stimuli in older populations.

Exercise-induced activation of STAT3 signaling is increased with age.

Activation of the transcription factor signal transducers and activators of transcription (STAT) 3 is common to many inflammatory cytokines and growth factors, with recent evidence of involvement in skeletal muscle regeneration. The purpose of this study was to determine whether STAT3 signaling activation is regulated differentially, at rest and following intense resistance exercise, in aged human skeletal muscle. Skeletal muscle biopsies were harvested from healthy younger (n = 11, 20.4 +/- 0.8 years) and older men (n = 10, 67.4 +/- 1.3 years) under resting conditions and 2 h after the completion of resistance exercise. No differences were evident at rest, whereas the phosphorylation of STAT3 was significantly increased in old (23-fold) compared to young (5-fold) subjects after exercise. This correlated with significantly higher induction of the STAT3 target genes including; interleukin-6 (IL-6), JUNB, c-MYC, and suppressor of cytokine signaling (SOCS) 3 mRNA in older subjects following exercise. Despite increased SOCS3 mRNA, cellular protein abundance was suppressed. SOCS3 protein is an important negative regulator of STAT3 activation and cytokine signaling. Thus, in aged human muscle, elevated responsiveness of the STAT3 signaling pathway and suppressed SOCS3 protein are evident following resistance exercise. These data suggest that enhanced STAT3 signaling responsiveness to proinflammatory factors may impact on mechanisms of muscle repair and regeneration.

Plasma amino acid response after ingestion of different whey protein fractions

Background and objectives The digestion rate of proteins and subsequent absorption of amino acids can independently modulate protein metabolism. The objective of the present study was to examine the blood amino acid response to whey protein isolate (WPI), β-lactoglobulin-enriched WPI, hydrolysed WPI and a flavour-identical control. Methods Eight healthy adults (four female, four male) were recruited (mean±standard error of the mean: age, 27.0±0.76 years; body mass index, 23.2±0.8 kg/cm2) and after an overnight fast consumed 500 ml of each drink, each containing 25g protein, in a cross-over design. Blood was taken at rest and then every 15 min for 2 h post ingestion. Results Ingesting the β-lactoglobulin-enriched WPI drink resulted in significantly greater plasma leucine concentrations at 45–120 min and significantly greater branched-chain amino acid concentrations at 60–105 min post ingestion compared with hydrolysed WPI. No differences were observed between WPI and β-lactoglobulin-enriched WPI, and all protein drinks resulted in elevated blood amino acids compared with flavour-identical control. Conclusions In conclusion, whole proteins resulted in a more rapid absorption of leucine and branched-chain amino acid into the blood compared with the hydrolysed molecular form of whey protein.

Whey protein ingestion activates mTOR-dependent signalling after resistance exercise in young men: a double-blinded randomized controlled trial.

The effect of resistance exercise with the ingestion of supplementary protein on the activation of the mTOR cascade, in human skeletal muscle has not been fully elucidated. In this study, the impact of a single bout of resistance exercise, immediately followed by a single dose of whey protein isolate (WPI) or placebo supplement, on the activation of mTOR signalling was analyzed. Young untrained men completed a maximal single-legged knee extension exercise bout and were randomized to ingest either WPI supplement (n = 7) or the placebo (n = 7). Muscle biopsies were taken from the vastus lateralis before, and 2, 4 and 24 h post-exercise. WPI or placebo ingestion consumed immediately post-exercise had no impact on the phosphorylation of Akt (Ser473). However, WPI significantly enhanced phosphorylation of mTOR (Ser2448), 4E-BP1 (Thr37/46) and p70S6K (Thr389) at 2 h post-exercise. This study demonstrates that a single dose of WPI, when consumed in modest quantities, taken immediately after resistance exercise elicits an acute and transient activation of translation initiation within the exercised skeletal muscle.