Human aging: effect on the activation of lymphocyte cyclic AMP-dependent protein kinase by forskolin

The effect of forskolin on freshly isolated human lymphocytes was characterized at the level of cyclic AMP-dependent protein kinase. Incubating lymphocytes in vitro with this potent adenylate cyclase activator led to time- and dose-dependent activation of protein kinase. The amount of activation varied with the conditions of enzyme preparation, suggesting that lymphocyte cyclic AMP-dependent protein kinase was artifactually activated unless special precautions were taken during its preparation. Under these conditions, forskolin-dependent protein kinase activation was greater in lymphocytes isolated from young compared to elderly human subjects. These results demonstrate coupling between lymphocyte cyclic AMP production and cyclic AMP-dependent protein kinase activation decreases in an age-related manner in man. This decrease resembles the loss of lymphocyte adenylate cyclase activity reported previously and occurs without other changes in lymphocyte protein kinase that were detectable using these methods. The age-related decrease in protein kinase activation is probably accounted for, therefore, by the age-related decrease in the cyclic AMP synthesizing capacity of the lymphocyte.