Lymphocytes freshly isolated from human subjects have ATP-dependent Na+ transport activity regulated by isoproterenol. The cells also have isoproterenol dependent adenylate cyclase activity which decreases with the age of the blood donor. Consequently, an important physiologic response (Na+ transport) which is mediated by the beta-adrenergic receptor may diminish with age in a readily accessible human disease. The biochemical pathways are probably cAMP mediated, in which case they include formation of the hormone-receptor complex; activation of the adenylate cyclase catalytic subunit; activation of cAMP-dependent protein kinases; phosphorylation of (membrane) protein which function in Na+ transport. Characterization of age-related changes in any of the components of the pathway can be accomplished using methdology in which we are already experienced. As a consequence, an indepth knowledge of the processes of aging in a human hormone target tissue can be achieved. Even though these changes may not be representative of those in every tissue, the results will provide insight into some cellular causes and consequences of age-related change and provide a foundation for eventually alleviating its undesirable effects.
| Krall, J F; Fernandez, E I; Connelly-Fittingoff, M (1987) Human aging: effect on the activation of lymphocyte cyclic AMP-dependent protein kinase by forskolin. Proc Soc Exp Biol Med 184:396-402 |
| Krall, J F; Fernandez, E I; Connelly-Fittingoff, M (1985) Lymphocyte protein kinase activity in cells from young and elderly men and women. Proc Soc Exp Biol Med 180:462-7 |
