Maintenance of the musculoskeletal mass by control of protein turnover: the concept of anabolic resistance and its relevance to the transplant recipient.

Although the overall size of the musculoskeletal mass is constrained by genetic limitations, both the day to day maintenance and muscle wasting and rehabilitation are regulated by protein synthesis (particularly the initiation and elongation stages of translation) and by protein breakdown. These are directly influenced by the nutritional state (size and composition of meals) and type, mode and duration of exercise. In the context of food-related changes, recent work has demonstrated that human muscle protein synthesis is almost entirely controlled by the availability of essential amino acids and protein breakdown by availability of insulin. Muscle protein synthesis is also markedly stimulated by preceding exercise in a manner independent of but additive to any effect of food. The sensing and signalling pathways within muscle are activated by food and exercise in normal healthy subjects to elevate net muscle balance for many hours after strenuous exercise. In many circumstances such as immobilisation, ageing and many chronic diseases of the lung, kidney, heart, etc (such as those often suffered by pre-transplant patients), the general debilitation includes muscle wasting. In these subjects there appears to be a general failure to respond adequately to food--so called "anabolic resistance". It seems highly likely that this circumstance will also apply to transplant recipients. It is also likely that anabolic resistance can be, to some extent, reversed by regular physical activity which may "tune up" the anabolic pathways to act in a more normal fashion. Nevertheless, the extent of re-growth and adaptation of composition of muscle in transplant patients could be hindered by drug treatment including the use of rapamycin (sirolimus) cyclosporine and corticosteroids. These predictions should be tested by examining longitudinal effects of different modes of exercise and nutritional regimens on rehabilitation of muscle in transplant patients.