The effect of donor age on human fibroblast beta-adrenergic receptor response and agonist-induced desensitization

Abstract

Aging has been associated with changes in beta-adrenergic receptor (beta-receptor) function in several tissues. The relative contribution of cellular aging and age-related changes in homeostatic regulation of receptor function is unknown. We have examined beta-receptor function in fibroblasts of young and old donors (young: mean age 31.2 ± 0.8 years ± S.E., n = 6; old; mean age 81.8 ± 0.6 years ± S.E., n = 6). Beta-rceptor responses to isoproterenol (ISO), (1 μM) were similar in the two groups. The concentration of ISO required for 50% maximal beta-receptor-mediated cyclic AMP production (EC 50) was similar in both groups. Fibroblast beta-receptor density was also similar in young and old groups. ISO-induced beta-receptor desensitization was both dose- and time-dependent. Sub-maximal desensitization by acute exposure (30 min) to ISO (1 mM) caused similar levels of beta-receptor desensitization in young (42.5 ± 2.5%) and old (42.8 ± 2.8%) groups and a similr increase in ISO EC 50. These findings demonstrate that aging in vivo does not cause changes in fibroblasts beta-receptor regulation that are retained in culture.