IMPACT OF AGING ON HSP70 ACCUMULATION AND THERMOTOLERANCE WITH HEAT STRESS:

1911 We and others have demonstrated that alterations in the heat inducible 72 kDa heat shock protein (HSP70) occur in both humans and animals undergoing heat stress. Thus, HSP70 may serve as a biomarker for tissues at risk from stressors such as hyperthermia. Interestingly, there is an age-associated attenuation in HSP70 accumulation following passive heat stress. The purpose of this study was to test the hypothesis that a reduction in cellular ability to mount an appropriate stress protein response in senescent rats following consecutive heating trials is associated with a decline in thermotolerance. We focused on the liver because previous data have demonstrated that this organ has the greatest increase in HSP70 accumulation in animals subjected to hyperthermia. Young (6-mo-old; n=10) and senescent (24 mo old; n=10) male Fischer 344 rats were heat stressed (colonic temperature of 41°C) twice, separated by 24 h. Heating rates were matched between days for each rat and the two age groups. Survival was monitored over the next 48 h. Liver samples were obtained upon death of a rat, or after the 48 h recovery period, and representative samples were then evaluated for total HSP70 levels. Thermal responses were similar between age groups for both heating trials. After the second heat stress, mortality was 40% in the senescent group but 0% in the young group. In comparisons between the two heat stressed groups, HSP70 levels were 59% lower (P<0.005) in the senescent vs. young rats that underwent similar heating protocols. These results indicate that reduced liver HSP70 accumulation in senescent rats following heat stress is associated with a decrease in thermotolerance. The data suggest that an aged organism has a diminished ability to properly maintain cellular function after thermal challenge. Supported by NIH AG12350, AG14687, and AR40771