The effect of age on β-adrenergic function in man: A review

The structure and function of the β-adrenergic adenylate cyclase complex in the elderly is reviewed. The function of the β-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 β-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 responsivenes in the elderly is due to a defect in the peripheral β-receptor-linked adenylate cyclase complex. The finding of reduced β-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 β-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 β-adrenergic responsiveness in the elderly are discussed.