Functional changes in GI motility associated with advanced age include slowing of gastric emptying, decreased peristalsis and slowing of colonic transit. These changes appear to be associated with region-specific loss of neurons as well as impaired function. The mechanism(s) underlying physiologic aging are likely to be multifactorial. Alterations in specific signal transduction pathways have been reported at the level of the receptor and post-receptor events including kinase expression and function, mitochondrial function and activation of the apoptosis cascade. Advanced age is associated with increased oxidative stress and its concomitant effects on cellular function. While no specific genes have been causally linked to life span in mammals, studies involving non-mammalian species suggest that specific genes are involved in determining life span and age-related changes in cellular function. Caloric restriction is the only intervention that has been shown to slow aging in a variety of species. Recent studies implicate a possible role for an insulin/insulin-like growth factor-1 cascade in the region-and tissue-specific changes associated with physiologic aging.