Schematic representation of the splicing of the human IGF-I gene in human muscle to produce human MGF (IGF-1Ec) as well as IGF-IEa and IGF-IEb. The IGF-I gene has two start sites located in or near exons 1 and 2. In response to a exercise/damage the IGF-I gene is first spliced to produce MGF. This involves a reading frame shift that results in the unique carboxy terminal sequence (E domain) of MGF (IGF-I Ec). The expression of the IGF-I gene is initiated by certain hormones, and this becomes a problem as during aging GH and testosterone levels decrease resulting in decreasing levels of the primary transcript so less can be spliced to MGF when the muscle is mechanically challenged. Also it appears that the mechanotransduction and signalling system that is upstream of the activation of the IGF-I gene also become less sensitive, and less MGF is produced.
