Moderate caloric restriction increases type 1 IGF receptors and protein synthesis in aging rats.

Insulin-like growth factor-1 (IGF-1) is an anabolic hormone that mediates the actions of growth hormone (GH) and is found at lower concentrations in aged animals. These decreases in GH and IGF-1 appear to have important physiological consequences for aging, since protein synthesis decreases with age, and administration of GH and/or IGF-1 has been shown to increase protein synthesis. The present study was designed to determine (a) the relationship between the age-related changes in rates of tissue protein synthesis and plasma IGF-1 concentrations, (b) type 1 IGF receptor density in tissues and (c) whether long-term moderate caloric restriction, which is known to increase life-span, affects these relationships. Male Brown Norway rats were fed ad libitum or caloric-restricted (60% ad libitum) from 14 weeks of age and sacrificed at different ages. In ad libitum fed animals there were age-related decreases in plasma IGF-1 concentrations (14%) and in the rates of protein synthesis of the heart (36%) and liver (38%). Type 1 IGF receptor density remained constant in all tissues with age. The caloric-restricted animals exhibited plasma IGF-1 concentrations 33 to 42% lower than the ad libitum fed animals. However, rates of protein synthesis increased by 70 and 30% in heart and diaphragm, and this increase was associated with 60 to 100% increases in type 1 IGF receptor densities when compared with ad libitum fed animals.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Effects of aging and dietary restriction on tissue protein synthesis: relationship to plasma insulin-like growth factor-1.

Insulin-like growth factor-1 (IGF-1) decreases with age in many species and appears to have an important role in the age-related decline in capacity for protein synthesis with age. The goals of these studies were to determine whether (a) ad libitum fed mice demonstrate age-related decreases in IGF-1, (b) the relationship between IGF-1 and age-related changes in protein synthetic capacity in ad libitum fed animals, and (c) whether moderate dietary restriction (which increases both life span and protein synthetic capacity) delays age-related changes in protein synthesis and plasma IGF-1. These studies indicate that (a) in ad libitum fed animals, plasma IGF-1 decreases with age between 10 and 15 months and moderate dietary restriction decreases plasma IGF-1 in young but not older animals, and (b) the temporal changes in protein synthesis are tissue specific; moderate dietary restriction either increases or prevents the age-related decline in tissue protein synthesis. Results suggest that in normal aging, decreases in IGF-1 are associated with the decline in protein synthesis but that other regulatory mechanisms appear to have an important role in this process. Dietary restriction decreases plasma IGF-1 in young animals and either increases protein synthesis or prevents the age-related decline in protein synthesis, suggesting that the effects of dietary restriction are not mediated via increases in plasma IGF-1.