According to the somatomedin model, growth hormone (GH)-dependent hepatic synthesis is responsible for maintaining circulating insulin-like growth factor (IGF)-I levels. On the other hand, the local autocrine/paracrine IGF-I expression in peripheral tissue is generally GH-independent and reflects the effects of various and tissue-specific trophic hormones. Circulating IGF-I levels undergo important age-related variations increasing at puberty and decreasing, thereafter, to low levels in the elderly. Low IGF-I levels in the elderly mainly reflect impaired somatotroph secretion but the decline in gonadal sex steroid levels, some protein and micronutrients malnutrition as well as age-dependent variations in IGF-binding proteins may also play a role in the age-related decrease in IGF-I activity. This, in turn, partially accounts for age-related changes in bones, muscles, cardiovascular system, central nervous system and the immune system. However, it is currently unclear whether treatment with exogenous IGF-I can retard or reverse age-related changes in body structure and function.
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