Genes that prolong life: Relationships of growth hormone and growth to aging and life span

Mutant mice with a combined deficiency of growth hormone (GH), prolactin, a nd thyrotropin, and knockout mice with GH resistance, live longer than thei r normal siblings. The extension of life span in these animals is very larg e (up to 65%) reproducible, and not limited to any particular genetic backg round or husbandry conditions. In addition to demonstrating that genes cont rol aging in mammals, these findings suggest that GH actions, growth, and b ody size may have important roles in the determination of life span. We des cribe the key phenotypic characteristics of long-living mutant and knockout mice, with an emphasis on those characteristics that may be related to del ayed aging in these animals. We also address the broader topic of the relat ionship between GH, growth, maturation, body size, and aging, and we attemp t to reconcile the well-publicized antiaging action of GH with the evidence that suppression of GH release or action can prolong life.