Effects of resistance exercise (intensity and volume) with or without leucine enriched protein supplementation on human myofibrillar protein synthesis and cell anabolic signalling

Sarcopenia or the involuntary age associated muscle wasting starts in the fourth decade of life and accelerates markedly from the fifth decade. This gradual loss of muscle mass eventually results in an inability of older people to carry out simple daily tasks, instability, is associated with an increased risk of falls and fractures, loss of independence, and reduced quality of life. As the number of older people is growing steadily in our society, this in turn places an increasing burden on health care resources, making the topic of sarcopenia and its consequences an important area for research. Resistance exercise and protein enriched feeding are potent stimulators of MPS and act synergistically to increase the MPS; however, the muscle protein synthetic responses to amino acids are blunted in the elderly in the resting state. Leucine has been shown to be the most potent branched-chain amino acid acting as a signal for accelerating MPS in the resting state. How intensity and duration of resistance exercise can affect MPS and anabolic signalling in the elderly is less well understood. Can leucine enriched protein supplementation coupled with resistance exercise rejuvenate the MPS responses in the elderly? We aimed to answer these questions. The results revealed a sigmoidal dose-response relationship between exercise intensity and the stimulation of MPS in the post absorptive state, with little increase from 20-40% 1RM, then a bigger rise at 60 % of 1 RM with no significant further increase up to 90% 1RM in both the young and the elderly. Both groups showed quantitatively similar increases in phosphorylation of both p70s6K and 4E-BP1, which were maximal for exercise at 60-90% 1 RM at 1 h post exercise, i.e. just before the maximal increase in MPS. However, older men demonstrated a blunted rise in MPS and anabolic signalling activity after exercise, suggesting a general pattern of a reduced protein synthetic response to exercise in the elderly. This may explain, in part the mechanisms through which muscle is lost gradually with ageing. Increasing exercise volume from 3 to 6 sets at 40% and 75% 1RM produced no additional MPS responses in post absorptive young men; however, in older men, it resulted in enhanced MPS and p70S6K responses at both intensities, suggesting that the muscle of older men requires a greater volume of exercise to activate the protein synthetic machinery sufficiently to achieve synthetic responses comparable to those seen in younger men. Exercise, irrespective of intensity and volume caused only short term stimulation in MPS (returned to basal level at 4h post exercise) in the post absorptive state. Leucine supplementation to protein feeding after resistance exercise appeared to overcome age-related anabolic blunting of responses of myofibrillar protein synthesis and p70S6K phosphorylation in skeletal muscle of older men by rejuvenating their synthetic responses. In summary, the results gave a clear indication as to the likely optimal exercise intensity and volume of acute resistance exercise (6 sets of 8-10 reps at 75% 1RM) coupled with optimal amino acid supplementation (leucine supplemented drink containing about 20 g of protein) required to effectively stimulate MPS and anabolic signalling in the elderly for maintenance of muscle mass. This work helps shed light on the pathophysiology of sarcopenia and suggests strategies that could be used to develop effective countermeasures to counteract sarcopenia.