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 media tes the actions of growth hormone (GH) and is found at lower concentra tions in aged animals. These decreases in GH and IGF-1 appear to have important physiological consequences for aging, since protein synthesi s decreases with age, and administration of GH and/or IGF-1 has been s hown to increase protein synthesis. The present study was designed to determine (a) the relationship between the age-related changes in rate s of tissue protein synthesis and plasma IGF-1 concentrations, (b) typ e 1 IGF receptor density in tissues and (c) whether long-term moderate caloric restriction, which is known to increase life-span, affects th ese relationships. Male Brown Norway rats were fed ad libitum or calor ic-restricted (60% ad libitum) from 14 weeks of age and sacrificed at different ages. In ad libitum fed animals there were age-related decre ases in plasma IGF-1 concentrations (14%) and in the rates of protein synthesis of the heart (36%) and liver (38%). Type 1 IGF receptor dens ity 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 associate d with 60 to 100% increases in type 1 IGF receptor densities when comp ared with ad libitum fed animals. These data suggest that alterations in tissue type 1 IGF receptors as well as availability of IGF-1 may be important factors in understanding the regulation of protein synthesi s by IGF-1 during aging or under conditions of long-term caloric restr iction.