The effect of age on beta-adrenergic function in man: a review.
The structure and function of the beta-adrenergic adenylate cyclase complex in the elderly is reviewed. The function of the beta-adrenergic receptor in man is modulated by levels of circulating catecholamines, noncatecholamine hormones, drugs, disease, and age. Although a number of clinical observations demonstrate an age-related decrease in catecholamine responsiveness, the molecular basis of this phenomenon is unknown. Simple reduction in beta-receptor number does not appear to explain age-associated loss of catecholamine responsiveness. Recent investigations from our laboratory employed salbutamol-induced rise in plasma cyclic AMP (cAMP) levels to study the molecular basis for this phenomenon. In young individuals there was a threefold increase in plasma cAMP levels after salbutamol infusion. In older subjects only a 50% rise in plasma cAMP levels was observed. These results suggest that the basis for reduced catecholamine responsiveness in the elderly is due to a defect in the peripheral beta-receptor-linked adenylate cyclase complex. The finding of reduced beta-adrenergic-stimulated adenylate cyclase activity in the aged prompted us to determine the specificity of this decline by measuring the activity in older and younger individuals of another hormone-sensitive adenylate cyclase. However, no effect of subject age was observed on glucagon-sensitive adenylate cyclase activity, suggesting that the blunted response of the beta-receptor adenylate cyclase complex in the elderly represents a specific loss of function and is not due to a general age-associated decline in hormone-stimulated cyclase function. Specific molecular defects which could account for decline in beta-adrenergic responsiveness in the elderly are discussed.
Ebstein
R P
RP
Stessman
J
J
Eliakim
R
R
Menczel
J
J
D000262:Adenylyl Cyclases / Q000502:physiology; D000328:Adult; D000368:Aged; D000375:Aging; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000494:pharmacology / Q000502:physiology; D000242:Cyclic AMP / Q000097:blood / Q000502:physiology; D005934:Glucagon / Q000494:pharmacology; D006801:Humans; D008214:Lymphocytes / Q000502:physiology; D008568:Memory / Q000502:physiology; D011898:Ranidae; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*
D002395:Catecholamines; D011943:Receptors, Adrenergic, beta; D005934:Glucagon; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D000420:Albuterol