Adult-Onset Growth Hormone and Insulin-Like Growth Factor I Deficiency Reduces Neoplastic Disease, Modifies Age-Related Pathology, and Increases Life Span

Disruption of the insulin/IGF-I pathway increases life span in invertebrates. However, effects of decreased IGF-I signaling in mammalian models remain controversial. Using a rodent model with a specific and limited deficiency of GH and IGF-I, we report that GH and IGF-I deficiency throughout life [GH deficiency (GHD)] has no effect on life span compared with normal, heterozygous animals. However, treatment of GHD animals with GH from 4–14 wk of age [adult-onset (AO) GHD] increased median and maximal life span by 14% and 12%, respectively. Analysis of end-of-life pathology indicated that deficiency of these hormones decreased tumor incidence in GHD and AO-GHD animals (18 and 30%, respectively) compared with heterozygous animals and decreased the severity of, and eliminated deaths from, chronic nephropathy. Total disease burden was reduced by 24% in GHD and 16% in AO-GHD animals. Interestingly, the incidence of intracranial hemorrhage increased by 154 and 198% in GHD and AO-GHD animals, respectively, compar...