Using a mouse model relevant for humans, lifespan can be prolonged by reducing IGF-I signaling selectively in the central nervous system. This effect occurred through changes in specific neuroendocrine pathways. Investigating the pathophysiological mechanism, we found that IGF receptors in the brain steered the development of the somatotropic axis, which in turn altered the individual growth trajectory and lifespan. Our work is experimental proof that chronically low IGF-I and low growth hormone (GH) levels favor long lifespan and postpone age-related mortality. Our results, together with other recent reports, challenge the notion that GH can slow down or prevent human aging. This is important because growth hormone is sometimes poposed to elderly people as a substitutive treatment in order to compensate the negative effects of aging. double dagger.