Rodent models of muscle wasting rarely display the underlying processes observed in human muscle wasting to be of much use heuristically. This is probably because of a greater metabolic stability of the human body than that observed in rodents. Thus the proper study of human age related muscle wasting has to be made in human beings. When this is done it is apparent that in the basal state, in healthy active persons between 50 and 80 y, there are few signs of derangements of muscle protein synthesis or breakdown or of increased markers of catabolic processes, possibly with the exception of increased signs of increased sub clinical inflammation in muscle. However there do appear to be major deficits in the ability of muscles from older persons to efficiently regulate the maintenance of their muscle during feeding. Dose response studies show that the hyperbolic relationship between myofibrillar protein synthesis and availability of essential amino acids amino acids is shifted down and to the right and that giving large amounts of amino acids is unable to overcome this anabolic resistance. Oddly postmenopausal women have a greater anabolic resistance than do older men. The anabolic resistance is also shown by the decreased phosphorylation of molecules in the PKB-mTOR-eIF4BP1 pathway in response to amino acid availability. The muscle synthetic system is refractory to amino acid provision irrespective of the availability of insulin, IGF-1 and growth hormone. On the other hand insulin is a major regulator of muscle protein breakdown in human muscle and we now have good evidence that there is blunting of the ability of older muscle to decrease proteolysis in response to low concentrations of insulin, such as those observed after light meals. The anabolic resistance of both arms of protein turnover is probably causally important in the slow development of sarcopenia. Simply providing more amino acids is not in my view a solution to the problem, and the most up to date nitrogen-balance data confirms the idea that the dietary protein requirements of older persons are not increased. What is needed is a way of retuning the muscles response to dietary protein. One way might be via exercise. Our recent work has shown that the sigmoidal dose response between muscle protein synthesis and resistance exercise intensity is shifted down wards 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 acutely overcome by increasing amino acid availability. Long tem bed rest also produces anabolic resistance of the whole body which cannot be overcome by feeding more protein. There is substantial interest in the proposition that a feature of anabolic resistance, including that of ageing is due to decrements in nutritive blood to human muscle. We have evidence that the blood flow responses to feeding and resistance exercise are less in the muscles of older persons and that they improve with resistance training. These improvements seem to be associated with better responses of muscle protein metabolism to food. However our understanding of the regulation of the size of the muscle mass with ageing and physical activity remains poor and a great deal more work is required to improve it.