Age-related muscle loss and progressive dysfunction in mechano sensitive growth factor signalling
G. Goldspink
Molecular Tissue Repair Unit, Department of Surgery, Royal Free and University College Medical School, Royal Free Campus, Rowland Hill Street, London NW3 2PF
Loss of muscle mass and function (sarcopenia) is one of the most marked
problems associated with ageing as it has major health care as well as
socioeconomic implications. The growth hormone/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.
Also there are local as well as systemic forms of IGF-I which have
different functions. We cloned two different IGF-Is that are expressed
by skeletal muscle and both are derived from the IGF-I gene by
alternative splicing. One of these 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
activating muscle satellite (stem) cells. Therefore, it appears these
two forms of IGF-I have different actions and that they are important
regulators of muscle growth. Growth hormone treatment apparently
upregulates the level of IGF-I gene expression and when it is combined
with resistance exercise more is spliced towards MGF. This results in
an increase in muscle cross sectional area in the elderly subjects who
otherwise would produce less MGF. The possibility of ameliorating
sarcopenia using MGF delivered as a peptide or by gene therapy will be
discussed.
Key words:
Sarcopenia, muscle mass, MGF, IGF-I, Exercise
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