Growth factors and muscle ageing

Abstract

Loss of muscle mass (sarcopenia) is one of the main problems associated with ageing as it has major health care as well as socioeconomic implications. The growth hormone (GH)/IGF-I axis is regarded as an important regulator of muscle mass. However, it is now appreciated that other tissues in addition to the liver express IGF-I and that there are local as well as systemic forms of IGF-I which have different functions. At least two different kinds of IGF-I that are expressed by skeletal muscle are derived from the IGF-I gene by alternative splicing, one of which is expressed in response to physical activity which has now been called 'mechano growth factor' (MGF). The other is similar to the systemic or liver type (IGF-IEa) and is important as the provider of mature IGF-I required for upregulating protein synthesis. MGF differs from systemic IGF-IEa in that it has a different peptide sequence which is responsible for replenishing the satellite (stem) cells in skeletal muscle. The ability to produce MGF declines with age, and this is commensurate with the decline in circulating GH levels. GH treatment up regulates the level of IGF-I gene expression in older people and when combined with resistance exercise more is spliced towards MGF and hence should improve the ability of muscle to respond to physical activity. The possibility of ameliorating sarcopenia using MGF is discussed.