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3
3
*
Department of Medicine, University of Wisconsin-Madison and Veterans Administration Hospital, Geriatric Research, Education and Clinical Center, Madison, WI 53705;
Wisconsin Regional Primate Research Center, University of Wisconsin, Madison, WI 53715;
**
Environmental Toxicology Center, University of Wisconsin, Madison, WI 53706 and
Departments of Genetics and Medical Genetics, University of Wisconsin, Madison, WI 53706
3To whom correspondence should be addressed. E-mail: rhweindr{at}facstaff.wisc.edu or taprolla{at}facstaff.wisc.edu
An active research area in biological gerontology concerns the mechanisms by which caloric restriction (CR) retards the aging process in laboratory rodents. We used high density oligonucleotide arrays representing 6347 genes to determine the gene expression profile of the aging process in gastrocnemius muscle of male C57BL/6 mice. Aging resulted in a differential gene expression pattern indicative of a marked stress response and lower expression of metabolic and biosynthetic genes. Most alterations were completely or partially prevented by CR. Transcriptional patterns of muscle from calorie-restricted animals suggest that CR retards the aging process by causing a metabolic shift toward increased protein turnover and decreased macromolecular damage. The use of high density oligonucleotide microarrays provides a new tool to measure biological age on a tissue-specific basis and to evaluate at the molecular level the efficacy of nutritional interventions designed to retard the aging process.
KEY WORDS: • caloric restriction • aging • gene expression • oligonucleotide microarrays • muscle
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