Alterations in Leukocyte β-Receptor Affinity with Aging

TLDR

Elderly individuals exhibit reduced β‑adrenergic sensitivity to agonists despite unchanged receptor density. The study examined how β‑receptor affinity for agonists varies with age in lymphocytes from 20 healthy men aged 21 to 74 years. Researchers measured the IC50 of isoproterenol in lymphocyte β‑receptors and compared high‑affinity receptor proportions in 12 subjects (six young, six older) in supine and upright positions. Affinity for agonists declined with age and correlated with plasma norepinephrine; older subjects had fewer high‑affinity receptors supine, and upright posture reduced high‑affinity receptors only in the young, suggesting reduced affinity underlies age‑related β‑adrenergic hyporesponsiveness. Published in N Engl J Med 1984; 310: 815–9.

Abstract

The elderly have reduced β-adrenergic sensitivity to agonists, but no change in receptor density. We investigated the relation between β-receptor affinity for agonists and age in β-receptors on lymphocytes from 20 healthy men 21 to 74 years old. As an index of β-receptor affinity for agonists, we determined the IC50 of isoproterenol — the concentration of isoproterenol required to inhibit 50 per cent of iodohydroxybenzylpindolol binding in vitro. We found that receptor affinity for agonists was correlated with age and plasma norepinephrine concentration. Twelve subjects (six 21 to 29 years old and six 55 to 74 years old) were also studied in both the supine and upright positions. In samples obtained in the supine position, the proportion of receptors binding agonist with a high affinity was decreased in the older subjects as compared with the young subjects (22±1 per cent vs. 38±3 per cent; P<0.05). With upright posture and the associated acute elevation of endogenous plasma catecholamines, the proportion of receptors binding agonist with a high affinity was reduced in the young; no such changes were seen in the older subjects. The data suggest that reduced β-receptor affinity for agonists may be an explanation for altered β-adrenergic sensitivity in the elderly. (N Engl J Med 1984; 310: 815–9.)