The regulation and mechanisms of action of growth hormone and insulin-like growth factor 1 during normal ageing.

The decrease in tissue function that is observed in ageing animals has been linked to the decline in rates of protein synthesis. These changes may be caused, in part, by reduced secretion of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). It is well established that growth hormone-releasing hormone (GHRH) and somatostatin have an important role in the regulation of GH secretion and results from several studies suggest that an age-related increase in release of somatostatin has an important role in altering the secretion of GH. When the amounts of somatostatin mRNA were examined, there was a decrease in the aged rats but the amount of somatostatin mRNA bound to polysomes increased in these animals. This suggests that translational regulatory mechanisms are compromised in ageing animals. Moderate dietary restriction, which has been shown to increase life span, increases the amplitude of GH pulses and the capacity of tissues to synthesize protein. We have used the caloric restriction model to investigate the regulation and roles of GH and IGF-1 during ageing. Our results suggest that neuroendocrine regulation of GH secretion plays an important role in the process of biological ageing and that part of the beneficial effects of moderate dietary restriction may be mediated by altering the GH, IGF-1 axis.