Cachexia, the illness-induced loss of skeletal muscle mass, is associated with an increase in morbidity and mortality. Unfortunately, even small and persistent changes in protein synthesis or protein degradation lead to large protein deficits because the rate of protein turnover is so high (240–310 g/day). 1 To date, there are no effective means of preventing or minimising this loss beyond aggressive treatment of the underlying illness. All is not gloomy, however, because losses in muscle mass can be regained with correction of the disorder. To improve prognosis, mechanisms that replenish protein stores and those that cause loss of muscle mass must be understood. Fortunately, progress is being made in both areas, but interpretation of the results is not sufficiently definitive to recommend therapies.

Skeletal muscle is composed of bundles of fibres bound together by collagen tissue. Each cell (fibre) consists of a membrane, many scattered nuclei lying under this membrane, and cytoplasm containing thousands of myofibrils. 2 Myofibrils consist of myosin and actin proteins that are arranged in sarcomeres; contraction occurs when actin slides towards the centre of the myosin scaffold. Although skeletal muscle fibres have multiple nuclei, these nuclei do not divide to produce new fibres. Instead, mononucleated satellite cells on the surface of muscle fibres divide and stimulate the fibres to synthesise the actin and myosin proteins that are needed to form new myofibrils. Accumulation of new myofibrils accounts for the sharp increase in muscle mass produced by exercise: weight training stimulates the synthesis of actin and myosin and the formation of myofibrils. Disuse of a muscle for 2 weeks reduces its size by 20%. 2 Important issues in muscle loss and its repair are how the process of restoring muscle mass can be started or accelerated, and whether loss of muscle mass can be prevented.