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, and thyrotropin, and knockout mice with GH resistance, live longer than their normal siblings. The extension of life span in these animals is very large (up to 65%), reproducible, and not limited to any particular genetic background or husbandry conditions. In addition to demonstrating that genes control aging in mammals, these findings suggest that GH actions, growth, and body size may have important roles in the determination of life span. We describe the key phenotypic characteristics of long-living mutant and knockout mice, with an emphasis on those characteristics that may be related to delayed aging in these animals. We also address the broader topic of the relationship between GH, growth, maturation, body size, and aging, and we attempt to reconcile the well-publicized antiaging action of GH with the evidence that suppression of GH release or action can prolong life.