Research studies clearly indicate that age-related changes in cellular and tissue function are linked to
decreases in the anabolic hormones, growth hormone and insulin-like growth factor (IGF)-1. Although there
has been extensive research on the effects of these hormones on bone and muscle mass, their effect on
cerebrovascular and brain ageing has received little attention. We have also observed that in response to
moderate calorie restriction (a treatment that increases mean and maximal lifespan by 30–40%), age-related
decreases in growth hormone secretion are ameliorated (despite a decline in plasma levels of IGF-1)
suggesting that some of the effects of calorie restriction are mediated by modifying the regulation of the
growth hormone/IGF-1 axis. Recently, we have observed that microvascular density on the surface of the
brain decreases with age and that these vascular changes are ameliorated by moderate calorie restriction.
Analysis of cerebral blood flow paralleled the changes in vasculature in both groups. Administration of
growth hormone for 28 d was also found to increase microvascular density in aged animals and further
analysis indicated that the cerebral vasculature is an important paracrine source of IGF-1 for the brain. In
subsequent studies, administration of GHRH (to increase endogenous release of growth hormone) or direct
administration of IGF-1 was shown to reverse the age-related decline in spatial working and reference
memory. Similarly, antagonism of IGF-1 action in the brains of young animals impaired both learning and
reference memory. Investigation of the mechanisms of action of IGF-1 suggested that this hormone regulates
age-related alterations in NMDA receptor subtypes (e.g. NMDAR2A and R2B). The beneficial role of
growth hormone and IGF-1 in ameliorating vascular and brain ageing are counterbalanced by their well-recognised
roles in age-related pathogenesis. Although research in this area is still evolving, our results
suggest that decreases in growth hormone and IGF-1 with age have both beneficial and deleterious effects.
Furthermore, part of the actions of moderate calorie restriction on tissue function and lifespan may be
mediated through alterations in the growth hormone/IGF-1 axis.