Age-associated decrease in beta-adrenergic receptors and adenylate cyclase activity in rat brown adipose tissue

Abstract

The ability to regulate body temperature diminishes with age. In the rat, nonshivering thermogenesis in brown adipose tissue (BAT) serves as the regulator of body temperature. This process is stimulated by catecholamine activation of adenylate cyclase through the beta-adrenergic receptor. However, beta-adrenergic responsiveness also diminishes with age. To investigate the age-related alterations in beta-adrenergic function in BAT, beta-adrenergic receptor number and cytochrome c oxidase activity were assessed in 3-, 12-, and 24-month-old rats, and adenylate cyclase activity was assessed in 3-, 12-, 18-, and 24-month-old rats. The amount of brown adipose tissue recovered from senescent rats was 30% less than that from either the 3- or 12-month-old rats. There was a corresponding decrease in the total amount of cytochrome c oxidase activity in the 24-month-old rats. In the senescent rats, the density of beta-adrenergic receptors was twofold less than in the 3- and 12-month-old rats. The decrease in density was predominately due to a decrease in the beta 1-adrenergic subtype. Isoproterenol- and NaF-stimulated adenylate cyclase activity were threefold greater and forskolin-stimulated activity was fourfold greater in the 3-month than in the older rats. There was no change in the Kact for isoproterenol with age. These biochemical alterations with age may contribute to the inability of older animals to thermoregulate when exposed to cold.