Anabolic resistance: the effects of aging, sexual dimorphism, and immobilization on human muscle protein turnover.

In healthy active older persons, there is no derangement of muscle protein metabolism. However, there is a major deficit in the ability of older muscles to regulate their maintenance during feeding and exercise. The dose-response relationship between myofibrillar protein synthesis and the availability of essential amino acids (EAA) is shifted down and to the right, and giving extra amino acids is unable to overcome this. There is no sex difference in basal or fed muscle protein metabolism in the young, but postmenopausal women have a greater anabolic resistance than older men. Anabolic resistance is also shown by the decreased phosphorylation in the PKB-mTOR-eIF4BP1 pathway in response to increased EAA. The muscle synthetic system is refractory to EAA provision, irrespective of the availability of insulin, insulin-like growth factor 1, and growth hormone. However, insulin is a major regulator of muscle protein breakdown, and there is a blunting of the ability of older muscle to decrease proteolysis in response to low concentrations of insulin, such as those observed after a light breakfast. Providing more EAA seems not to be useful, and modern N-balance data confirm that the dietary protein requirements of older persons are not increased. The sigmoidal dose-response relationship between muscle protein synthesis and resistance exercise intensity is shifted downward and to the right in older men. Decreased physical activity itself, even in young subjects, can produce anabolic resistance of muscle protein synthesis, which cannot be overcome by increasing amino acid availability. Exercise may retune the amino acid and (or) insulin sensitivity of muscle in older people.