RELATIONSHIP BETWEEN COLD-INDUCED THERMOREGULATION AND SPONTANEOUS RAPID BODY-WEIGHT LOSS OF AGING F344 RATS

We previously showed that, although cold-induced thermoregulation is a ttenuated in 26-mo-old male Fischer 344 (F344) rats, not all rats this age exhibit the same degree of cold-exposed hypothermia or diminished brown adipose tissue nonshivering thermogenic capacity. Examination o f this heterogeneity suggested the hypothesis that it associated with a difference in the physiological state between aged rats that were ma intaining stable body weight versus those showing the rapid weight los s often occurring near the end of the rat's natural life span. To test this, we acutely exposed male F344 rats to cold (4 h at 6 degrees C) beginning at 24 mo of age. This exposure was weekly for the first 2 wk and then on alternate weeks as long as the rat's body weight was stab le. If body weight progressively declined for 3-5 consecutive days, th e rat's response to the acute cold exposure was again measured, as was that of two additional rats not displaying this rapid loss in body we ight. If body temperature decreased during the cold exposure to intrap eritoneal temperatures less than or equal to 32.5 degrees C, the rat w as killed with pentobarbital sodium and interscapular brown adipose ti ssue was removed. One of the age-matched controls was also killed at t his time. The age at which body weight showed a spontaneous rapid decl ine ranged from 24.5 to 29 mos. All eight rats displaying spontaneous rapid weight loss had significant hypothermia during the acute cold ex posure, whereas none of the eight weight-stable rats did. The developm ent of hypothermia in the spontaneous rapid weight loss group was not, in general, observed before their weight loss. The weight loss and hy pothermia were associated with lower levels of brown fat uncoupling pr otein and significant changes in body fat and protein. These data sugg est that the development of senescence-related hypothermia occurs rapi dly and is not a simple function of chronological age or the median li fe span of the animals. Furthermore, these data imply that the rate of aging in terms of maintenance of thermoregulatory homeostasis has bot h a gradual and rapid component, the latter being associated with a di fferent physiological state than the former.