Although the old saw tells us that old age does not come alone, it is discomforting to see our physical capacity dwindling: the prospect of struggling to rise from a chair (or, heaven forbid, the toilet!) is not a pleasant one. Age-related muscle wasting may start as early as the fourth decade and occurs at 0.5–2% per year. The underlying mechanisms are a mystery, although we all know individuals who remain preternaturally young: as well as genetic predisposition, environmental influences, probably including imprinting, are probably very important. Among these, of course, is eating. Since it was realized (Volpi et al. 2001) that initially reported decrements in the basal rate of muscle protein synthesis in elderly people were unfeasibly large, the focus of many of us interested in age-related sarcopenia has turned to the ability of old muscle to respond appropriately to food. In human beings, a meal roughly doubles protein synthesis (Rennie et al. 1982) and most of this effect is due to the stimulatory effects of amino acids (Bennet et al. 1989), particularly branched chain amino acids and particularly leucine (Smith et al. 1992). Oddly, insulin has a negligible effect in modulating muscle protein synthesis in the presence of amino acids (Greenhaff et al. 2005) although there may be a requirement for a small, permissive amount of insulin for the amino acids to signal appropriately. However, the stimulation of protein synthesis is not the entire story and muscle protein breakdown falls as a result of a meal and here previous evidence suggests that the major player is not leucine but insulin, which markedly inhibits muscle protein breakdown. By and large the amplitude of the meal-related increase in protein synthesis is greater than the meal-related depression of protein breakdown but the two combine to replace protein which is lost in the post-absorptive period, during the diurnal cycle. It is now apparent that both in rats and human beings ageing is associated not so much with decrements and basal rates of protein turnover but in an inability to mount appropriate anabolic responses to feeding – what we have termed anabolic resistance (Cuthbertson et al. 2005). This is shown by a decreased sensitivity and responsiveness of protein synthesis in the muscle of old rats and men aged 60–70 and this is itself apparently due to decreased sensing and signalling activity in aged muscle (Guillet et al. 2004; Cuthbertson et al. 2005). Some time ago the late Bernard Beaufrere and co-workers demonstrated that whole body proteolysis appeared to be more resistant to the effects of insulin in older individuals (Boirie et al. 2001), which is obviously pertinent to the question of anabolic resistance of protein breakdown after food. Now Didier Attaix and his group (Combaret et al. 2005) have attempted to unravel the mechanisms of the postprandial blunting of the normal inhibition of protein synthesis using old (22 month) and young (8 month) rats. They confirm, in a paper published in this issue of The Journal of Physiology that by a number of indices the normal feeding-related fall of muscle protein breakdown is less in the old rats. Remarkably, what they have shown is that when old rats are fed a diet which is supplemented with leucine, there is what amounts to a rejuvenation of the normal postprandial inhibition of muscle protein breakdown. This is exciting because it strengthens the idea of a co-ordinated linkage between the meal-related stimulation of protein synthesis (via a pathway involving PKB/mTOR/p70S6 kinase) and the inhibition of the MAFbx component of the ubiquitin-dependent proteasome proteolytic pathway. Although the authors did not test the possibility, it may be that leucine also does something to sharpen up the sensitivity of muscle proteolysis to insulin – something which obviously needs to be tested. What does this tell us about preserving our shrinking muscles? As the lean body mass declines older people need less dietary energy – and cutting down on dietary fat and high glycaemic-index carbohydrates is obviously a good idea for health reasons. However, in addition, although we probably do not need to eat more protein it makes sense that what we do eat is of high quality, and that probably means animal protein, which contains lots of leucine.
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Mar 6, 2010
Ahmed Ghaly + 1
Open Access