Looking at IGF-1 through the hourglass

The role of insulin-like growth factor 1 (IGF-1) in human aging has been hotly debated. IGF-1, a central regulator of growth, plays a critical function in development and energy investment. For instance, the absence of functional IGF-1 or IGF-1 receptors in the central nervous system leads to severe developmental abnormalities, whereas reduction in circulating IGF-1 level, which is regulated by growth hormone (GH), results in small whole-body size [1]. In contrast, during aging, circulating IGF-1 may become dispensable or even detrimental. In fact, reduced long-term GH/IGF-1 improves the lifespan and health of numerous model organisms, including nematode worms, fruit flies, and mice. Despite strong evidence for beneficial effects of diminished GH/IGF-1 signaling in aging models, human studies investigating IGF-1’s role in aging and age-associated diseases have been discrepant and until recently it has not been possible to reconcile the inconsistent results.