Insulin-like growth factor-1 stimulation of protein synthesis is attenuated in cerebral cortex of aging rats

It has been postulated that brain aging and the accompanying neurodegenerative processes associated with aging result from a deterioration of mechanisms that regulate the maintenance of basic cellular processes. In the present study, it was hypothesized that decreased availability and/or diminished responsiveness of tissues to growth factors such as insulin-like growth factor-1 may be partly responsible for decreases in total protein synthesis previously observed in aging animals. Male Brown Norway rats (5-7 and 27-28 months old) were used to determine (1) whether in vivo protein synthesis in cortex, hippocampus, hypothalamus and cerebellum decreases with age and (2) whether these deficiencies are associated with age-related alterations in response to insulin-like growth factor-1, des (1-3) IGF-1 or insulin. Analysis of in vivo protein synthesis rates revealed a decline of 20% in cortex of old rats (P < 0.05) but no changes were observed in hippocampus, hypothalamus, or cerebellum. Stimulation of cortical slices in vitro with insulin-like growth factor-1, des (1-3) insulin-like growth factor-1, or insulin increased protein synthesis rates in young animals, but the response to these growth factors was blunted in old animals. Analysis of type 1 insulin-like growth factor receptor densities by quantitative autoradiography demonstrated age-related decreases in receptor levels in cerebellar cortex and dentate gyrus of the hippocampus but no changes in cortex. Regional distribution of type 1 insulin-like growth factor receptors within each of these tissues did not appear to change with age.(ABSTRACT TRUNCATED AT 250 WORDS)