Reduced somatotropic [growth hormone (GH) and insulin-like growth factor-1 (IGF-1)] action has been associated with delayed and slower aging, reduced risk of frailty, reduced age-related disease and functional decline, and with remarkably extended longevity. Recent studies have added to the evidence that these relationships discovered in laboratory populations of mice apply to other mammalian species. However, the relationship of the somatotropic signaling to human aging is less striking, complex and controversial. In mice, targeted deletion of GH receptors (GHR) in the liver, muscle or adipose tissue affected multiple metabolic parameters but failed to reproduce the effects of global GHR deletion on longevity. Continued search for mechanisms of extended longevity in animals with GH deficiency or resistance focused attention on different pathways of mechanistic target of rapamycin (mTOR), energy metabolism, regulation of local IGF-1 levels and resistance to high-fat diet (HFD).