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Biochemical, Molecular, and Genetic Mechanisms

- and -Tocopherol Prevent Age-Related Transcriptional Alterations in the Heart and Brain of Mice^1–3,

⁴ Department of Genetics and Medical Genetics, and ⁵ Veterans Administration Hospital, Department of Medicine and Wisconsin Primate Research Center, University of Wisconsin, Madison, WI 53706; ⁶ Department of Biostatistics, Section on Statistical Genetics and Clinical Nutrition Research Center, University of Alabama, Birmingham, AL 35294; and ⁷ Vascular Biology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111

^* To whom correspondence should be addressed. E-mail: taprolla{at}wisc.edu.

We used high-density oligonucleotide arrays to measure transcriptional alterations in the heart and brain (neocortex) of 30-mo-old B6C3F₁ mice supplemented with -tocopherol (T) and -tocopherol (T) since middle age (15 mo). Gene expression profiles were obtained from 5- and 30-mo-old control mice and 30-mo-old mice supplemented with T (1 g/kg) or a mixture of T and T (500 mg/kg of each tocopherol) from middle age (15 mo). In the heart, both tocopherol-supplemented diets were effective in inhibiting the expression of genes previously associated with cardiomyocyte hypertrophy and increased innate immunity. In the brain, induction of genes encoding ribosomal proteins and proteins involved in ATP biosynthesis was observed with aging and was markedly prevented by the mixture of T and T supplementation but not by T alone. These results demonstrate that middle age-onset dietary supplementation with T and T can partially prevent age-associated transcriptional changes and that these effects are tissue and tocopherol specific.