Pleiotropic Effects of Growth Hormone and Insulin-like Growth Factor (IGF)-1 on Biological Aging: Inferences From Moderate Caloric-Restricted Animals

Abstract

Moderate caloric restriction (60% of ad libitum intake) is an important model to investigate potential mechanisms of biological aging. This regimen has been reported to decrease the number of pathologies and increase life span in all species tested to date. Although moderate caloric restriction induces a wide range of physiological changes within the organism, adaptive changes within the endocrine system are evident and serve to maintain blood levels of glucose. These alterations include an increase in growth hormone secretory dynamics and a decline in plasma levels of IGF-1. These endocrine compensatory mechanisms can be induced at any age, and we have proposed that these alterations mediate some of the beneficial aspects of moderate caloric restriction. Numerous studies indicate that growth hormone and IGF-1 decrease with age and that administration of these hormones ameliorates the deterioration of tissue function evident in aged ad libitum-fed animals, suggesting that the absence of these hormones contributes to the phenotype of aging. Nevertheless, IGF-1 is an important risk factor in age-related pathologies including lung, breast, and prostate cancer. From these studies, we propose that endocrine compensatory mechanisms induced by moderate caloric restriction (including increased growth hormone and decreased IGF-1) decrease the stimulus for cellular replication, resulting in a decline in pathologies and increased life span observed in these animals. These findings have important implications for potential mechanisms of moderate caloric restriction and suggest that neuroendocrine compensatory mechanisms exert a key role on the actions of moderate caloric restriction on life span.

Caloric restriction and intermittent fasting: Two potential diets for successful brain aging

“…Thus alterations in the capacity to activate the PI3K/Akt pathways can have dramatic effects upon cell survivability and this process may be critical in transferring the positive effects of CR/IF to the organism. CR uncouples insulin/IGF-I signaling to FoxO factors by markedly reducing plasma IGF-I and insulin levels in rats (Sonntag et al, 1999). These decreases in circulating insulin/IGF-I levels result in decreased Akt phosphorylation in liver and decreased PI3K expression in muscle (Argentino et al, 2005).…”

Growth hormone therapy and Quality of Life: possibilities, pitfalls and mechanisms

“…Moreover, GH administration has been shown to increase vascular density in the ageing rat cortex . The effect of exogenous GH can be mimicked by caloric restriction, which prevents the age-related decline in GH (Lynch et al 1999). Cerebral IGF-I is increased whereas peripheral IGF-I is decreased following caloric restriction (Sonntag et al 1999), suggesting that local IGF-I may mediate cerebral angiogenic actions of GH.…”

IGF-1 has sexually dimorphic, pleiotropic, and time-dependent effects on healthspan, pathology, and lifespan

“…Decreased growth hormone and IGF-1 levels throughout life have been shown to increase lifespan in several model systems, including Caenorhabditis elegans, Drosophila, and dwarf mice (Bansal et al 2015;Bartke et al 2000;Brown-Borg et al 1996;Richardson et al 2004;Rincon et al 2005;Sonntag et al 1999Sonntag et al , 2005. Within the dwarf mice, decreased incidence of cancer and reduced cancer metastasis likely contribute to the observed lifespan extension (Bartke and Brown-Borg 2004;Ikeno et al 2003Ikeno et al , 2009).…”

“…A majority of the studies suggesting that reduced IGF-1 is beneficial for aging are based on models that exhibit a constitutive deficiency of IGF-1 beginning early in life (Bansal et al 2015;Bartke et al 2000;Brown-Borg et al 1996;Richardson et al 2004;Rincon et al 2005;Sonntag et al 1999Sonntag et al , 2005. Based on models that restore IGF-1 levels late in life, other studies have suggested that the age-related loss in IGF-1 is detrimental for aging (Markowska et al 1998;Ramsey et al 2004;Sonntag et al 2000).…”