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J Appl Physiol (November 2, 2001). doi:10.1152/japplphysiol.00733.2001
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Articles in PresS, published online ahead of print November 2, 2001
J Appl Physiol, 10.1152/jap.00733.2001
Submitted on July 13, 2001
Accepted on October 30, 2001

Differential Expression of Stress-Related Genes with Aging and Hyperthermia

Hannah J Zhang1, Victoria J Drake1, Joanna P Morrison1, Larry W Oberley2, and Kevin C Kregel1*

1 Exercise Science, The University of Iowa, Iowa City, IA, USA
2 Radiation Oncology, The University of Iowa, Iowa City, IA, USA

* To whom correspondence should be addressed. E-mail: kevin-kregel{at}uiowa.edu.

Aging is associated with a reduced capacity to cope with physiological stress. To study the molecular mechanisms associated with the decline in stress tolerance that accompanies aging, differences in gene expression between young and old Fisher 344 rats under euthermic control conditions or in response to hyperthermic challenge were evaluated using a cDNA array containing 207 stress-related genes. In the non-stressed control condition, aging resulted in selective up-regulation of stress protein genes and transcripts involved in cell growth, death and signaling, along with a down-regulation of genes involved in antioxidant defenses and drug metabolism. Heat stress resulted in a broad induction of genes in the antioxidant and drug metabolism categories and transcripts involved in DNA, RNA and protein synthesis for both age groups. Old animals had a robust up-regulation of genes involved in cell growth, death and signaling after heat challenge, along with a blunted expression of stress response genes. In contrast, young animals had a strong induction of stress response genes after hyperthermic challenge. Changes in expression of selected genes were confirmed by RT-PCR analysis. These findings suggest that aging results in altered gene expression in response to heat stress that is indicative of decreased stress protein transcription and increased expression of oxidative stress-related genes. Thus, our findings support the postulate that transcriptional changes in response to a physiological challenge such as hyperthermia contribute to the loss of stress tolerance in older organisms.




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