Pleiotropic effects of growth hormone and insulin-like growth factor (IGF)-1 on biological aging: Inferences from moderate caloric-restricted animals

Moderate caloric restriction (60% of ad libitum intake) is an important mod el to investigate potential mechanisms of biological aging This regimen has Been reported to decrease the number of pathologies and increase life span in ad species tested to date. Although moderate caloric restriction induce s a wide range of physiological changes within the organism, adaptive chang es within the endocrine system are evident and serve to maintain blood leve ls of glucose. These alterations include an increase in growth hormone secr etory dynamics and a decline in plasma levels of IGF-1. These endocrine com pensatory mechanics call be induced at any age, and we have proposed that t hese alterations mediate some of the beneficial aspects of moderate caloric restriction. Numerous studies indicate that growth hormone and IGF-1 decre ase with age and that administration of these hormones ameliorates the dete rioration of tissue function evident in aged ad libitum-fed animals, sugges ting that the absence of these hormones contributes to the phenotype of agi ng, Nevertheless, IGF-1 is an important risk factor in age-related patholog ies including Icing, breast, and prostate cancer. From these studies, we pr opose that endocrine compensatory mechanisms induced by moderate caloric re striction (including increased growth hormone mid decreased IGF-1) decrease the stimulus for cellular replication, resulting ill a decline ill patholo gies and increased life span observed ill these animals. These findings hav e important implications for potential mechanisms of moderate caloric restr iction and suggest that neuroendocrine compensatory mechanisms exert a key role on the actions of moderate caloric restriction on life span.