Age-related decline in beta adrenergic and adenosine A1 receptor function in the heart are attenuated by dietary restriction

Previously published reports from this laboratory have shown that the antiadrenergic effect of adenosine A, agonists declines with age in the rat heart [Gao et al. (1997) J Mol Cell Cardiol 29:593-602] and that this decline may be caused by a decrease in coupling between adenosine A(1) receptors (AdoA(1)R) and guanine nucleotide-binding proteins [Cai et al. (1997) Circ Res 81:1065-1071]. Dietary restriction (DR; 60% calories of ad libitum) has been shown to attenuate age-related changes in cellular signal transduction pathways. Therefore, the present study investigated whether DR altered the age-related changes in AdoA(1)R-mediated function in senescent rat hearts. Ventricular membranes were isolated from the hearts of ad libitum (AL) fed and DR male F344 rats that were 6, 12 and 24 months of age. In AL rats, there was an age-related decline in isoproterenol (ISO)-stimulated adenylyl cyclase when compared with the 6-month-old rats. The decline in ISO-stimulated cyclase was attenuated in DR animals. In AL rats, inhibition of ISO-stimulated adenylyl cyclase by the AdoA(1) R agonist, N-6-p-sulfophenyladenosine (SPA) decreased with age. In DR rats, the age-related decline in inhibition was attenuated. Previous results from this laboratory indicated that in AL fed rats, there was an age-related decrease in the percentage of high-affinity binding sites for SPA, from 55% at 6 months to 23% at 24 months. Diet restriction attenuated this age-related shift in high-affinity binding sites so that the percentage of high-affinity sites at 24 months was 42%. Our results suggest that DR maintains AdoA(1)R function by preventing a loss of high-affinity AdoA(1)R sites.