Heat and a variety of other damaging agents are known to induce the expression of a set of highly conserved proteins known as the heat shock proteins (HSPs). These proteins, which appear to be critical for cellular homeostasis, have been studied extensively in cultured cells, but relatively little is known concerning their expression in vivo. In-this project we are examining the expression of HSPs in rodents in response to physiological stresses in vivo. Particularly focusing on the HSP response in aging. Previously, we demonstrated that HSP70 expression was impaired in cultured fibroblasts from aged rats relative to those of young rats. We also demonstrated that HSP70 expression was reduced in aged animals, subjected to heat stress in vivo, but the diminished response appeared to be secondary to alterations in thermoregulation. over the past year we have shown that in mice HSP70 expression is also induced in brown fat (the major heat generating organ) in response to cold stress. Again, an age-related decline in the expression is apparent and appears to be the result of at least in part, altered thermoregulation. More recently, we have observed that HSP70 is also induced in response to restraint stress in rats. Two important features of this response are that the induction is relatively specific to the adrenal gland and involves the selective expression of one particular gene transcript. These findings along with our previous observations of specific localized HSP70 expression in regions of the brain associated with the neuroendocrine axis suggest a link between this cellular response to stress and the classical hormonal stress response.