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,
* Department of Exercise Science,
The Free Radical Research Institute, and
Radiation Research Laboratory, The University of Iowa, Iowa City, Iowa 52242, USA;
§ Department of Internal Medicine, University of New Mexico, New Mexico 87131, USA;
|| Pathology and Laboratory Medicine Service, VA Hospital, Madison, and Department of Pathology, University of Wisconsin Medical School, Madison, Wisconsin 53705, USA; and
Department of Medicine, University of Wisconsin and Veterans Administration Geriatric Research, Education and Clinical Center, Madison, Wisconsin 53705, USA
1Correspondence: Integrative Physiology Laboratory, 532 FH, The University of Iowa, Iowa City, IA, 52242. E-mail: kevin-kregel{at}uiowa.edu
Adult-onset, long-term caloric restriction (CR) prolongs maximum life span in laboratory rodents. However, the effect of this intervention on an organism’s ability to cope with a physical challenge has not been explored. We investigated the influence of CR and aging on stress tolerance in old rats exposed to an environmental heating protocol on two consecutive days. We hypothesized that CR would increase heat tolerance by reducing cellular stress and subsequent accrual of oxidative injury. All calorically restricted rats survived both heat exposures compared with only 50% of their control-fed counterparts. CR also decreased heat-induced radical generation, stress protein accumulation, and cellular injury in the liver. In addition, heat stress stimulated marked induction of the antioxidant enzymes manganese-containing superoxide dismutase and catalase, along with strong nuclear catalase expression in liver samples from rats subjected to CR. In contrast, stress-related induction of antioxidant enzymes was blunted, and nuclear catalase expression was unchanged from euthermic conditions in the control-fed group. These data suggest that CR reduces cellular injury and improves heat tolerance of old animals by lowering radical production and preserving cellular ability to adapt to stress through antioxidant enzyme induction and translocation of these proteins to the nucleus.—Hall, D. M., Oberley, T. D., Moseley, P. M., Buettner, G. R., Oberley, L. W., Weindruch, R., Kregel, K. C. Caloric restriction improves thermotolerance and reduces hyperthermia-induced cellular damage in old rats.
Key Words: free radicals • oxidative stress • stress proteins • HSP70 • aging • antioxidant enzymes
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