Could a deficiency in growth hormone signaling be beneficial to the aging brain?

Several studies have shown that growth hormone (GH)-deficient/resistant animals have a prolonged lifespan compared with their normal siblings. Studies in our laboratory have suggested that both Ames dwarf and GH receptor/GH binding protein knockout (GH-R-KO) mice do not experience age-induced cognitive aging at the same rate as their normal siblings. The studies presented here were aimed at determining whether these long-lived mice experience a delay in age-related changes in behavior. Young and old mice of both strains were tested in an open-field task. In addition, mice of the GH-R-KO strain were tested in the water maze to confirm previous findings using the inhibitory avoidance task that suggested delayed cognitive aging. In each of these studies, normal (wild-type) animals of the same age, sex, and genetic background as the mutants served as controls. Old GH-R-KO mice did not experience the decline in locomotor activity or difference in activity levels in the open-field task seen in the normal animals. Young normal and young and old Ames dwarf mice spent less time in the center of the apparatus compared with old normal animals. There were no signs of age-related changes in emotionality within the GH-R-KO strain. Water maze results also showed that while old normal animals performed poorer than the young normal animals, old GH-R-KO mice did not perform differently from the young normal or young GH-R-KO groups. Taken together, these studies support our previous findings of delayed age-induced cognitive and behavioral decline in GH deficient/resistant mice.