Age-Related Decreases in Growth Hormone and Insulin-Like Growth Factor (IGF)–1: Implications for Brain Aging

There is abundant empirical and scientific evidence to support the hypothesis that functional deterioration of tissue with age is closely related to a decline in hormone concentrations and/or hormone action, but the specific etiology and/or consequences of these deficiencies remain elusive. Growth hormone (GH) and insulin-like growth factor–1 (IGF-1) are two potent anabolic hormones that decrease with age, and contribute to the loss in tissue function associated with normal aging. In this review, (1) basic age-related changes in the regulation of these hormones are detailed and information related to mechanisms of tissue resistance to GH are presented; (2) the potential use of GH as a therapeutic intervention to delay physiological changes associated with age is discussed; and (3) current information on the relationship among GH, IGF-1, microvascular rarefaction, and brain aging is detailed. Finally, our findings of beneficial actions of GH and IGF-1 are reconciled with other investigators using dwarf models of GH/IGF-1 deficiency, suggesting that these hormones delay age-related changes in both cognitive function and lifespan. We conclude that deficiencies in GH and IGF-1 contribute to the functional decline in tissues with age, especially related to brain aging. In addition, we provide evidence that Ames and Snell dwarf models are compromised by multiple endocrine deficiencies, developmental anomalies, and potentially moderate caloric restriction, which compromise them as models of GH and IGF-1 deficiency.