Decreases in plasma IGF-1 levels that occur with age have been hypothesized to contribute to the genesis of brain aging. However, support for this hypothesis would be strengthened by evidence that growth hormone/IGF-1 deficiency in young animals produce a phenotype similar to that found in aged animals. As a result, we developed a unique model of adult-onset growth hormone/IGF-1 deficiency, using dwarf rats specifically deficient in growth hormone and IGF-1. The deficiency in plasma IGF-1 is similar to that observed with age (e.g. 50% decrease) and replacement of growth hormone restores levels of IGF-1 to that found in normal (young) animals. The current study employs this model to investigate the effects of circulating growth hormone and IGF-1 on local cerebral glucose utilization (LCGU). Analysis of LCGU indicated that growth hormone/IGF-1 deficient animals exhibited a 29% decrease in glucose metabolism in many brain regions, especially those involved in hippocampally-dependent processes of learning and memory. Similarly, a high correlation between plasma IGF-1 levels and glucose metabolism was found in these areas. The deficiency in LCGU was not associated with alterations in GLUT1, GLUT3 or hexokinase activity. A 15% decrease in ATP levels was also found in hippocampus of growth hormone deficient animals providing compelling data that circulating growth hormone and IGF-1 have significant effects on the regulation of glucose utilization and energy metabolism in the brain. Furthermore, our results provide important data to support the conclusion that deficiencies in growth hormone/IGF-1 contribute to the genesis of brain aging.