EFFECTS OF AGE, GENDER, AND SENESCENCE ON BETA-ADRENERGIC RESPONSES OF ISOLATED F344 RAT BROWN ADIPOCYTES IN-VITRO

We previously reported greater age-related attenuation of cold-induced thermoregulation and brown adipose tissue thermogenic capacity in mal e vs. female F344 rats. With onset of the rapid weight loss that occur s near the end of the lifespan, this age-related attenuation becomes s evere. We refer to this ''end-of-life'' physiological state of older r ats as senescence. Here, we measured oxygen consumption of isolated br own adipocytes and found no age (6 vs. 12 vs. 26 mo) or gender effects on maximal norepinephrine (NE)- or CL-316,243 (beta(3)-adrenergic ago nist)-induced responses. In contrast, brown adipocytes from 22- to 26- mo-old senescent rats (males and females) consumed 51-60% less oxygen during maximal stimulation with NE and CL-316,243 than did cells from 26-mo-old presenescent rats. This attenuation was associated with lowe r (65-72%) uncoupling protein 1 concentrations but no alterations in N E-induced cAMP levels or lipolysis. Our data indicate that senescence, but not chronological age, significantly impacts NE-/beta(3)-mediated thermogenesis of isolated brown adipocytes and that this effect invol ves altered mitochondrial rather than altered membrane or cytosol even ts.