alpha- and gamma-Tocopherol prevent age-related transcriptional alterations in the heart and brain of mice

Abstract

We used high-density oligonucleotide arrays to measure transcriptional alterations in the heart and brain (neocortex) of 30-mo-old B6C3F(1) mice supplemented with alpha-tocopherol (alphaT) and gamma-tocopherol (gammaT) 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 alphaT (1 g/kg) or a mixture of alphaT and gammaT (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 alphaT and gammaT supplementation but not by alphaT alone. These results demonstrate that middle age-onset dietary supplementation with alphaT and gammaT can partially prevent age-associated transcriptional changes and that these effects are tissue and tocopherol specific.

FIGURE 1. The global analysis of the effect of vitamin E supplementation on age-related transcriptional changes in the mouse heart and brain

1,258 genes that were significantly changed with normal aging in the heart (A and B), and 8,523 genes in the neocortex (C and D) are displayed. The fold change (FC) of old control vs. young control (age), and old vitamin E-supplemented group vs. old control (α-T = α-tocopherol (A and C), α/γ-T = α- and γ-tocopherol (B and D)) comparisons are shown in x- and y-axis, respectively. Red dots: significantly different between vitamin E-supplemented group and old control group (p-value < 0.05).

FIGURE 2. Real-time quantitative RT-PCR analysis of a subset of genes in the heart and brain

A. The influence of aging and vitamin E treatment in heart. Actin, alpha 1 (Acta1); mitochondrial ribosomal protein L34 (Mrpl34); procollagen XVIII, alpha 1 (Col18a1); cardiotrophin 1 (Ctf1); phenylalanine hydroxylase (Pah); p53; p16. B. The effect of aging and vitamin on selected genes altered in brain aging. Complement component 4 (C4); P lysozyme structural (Lzp-s);glial fibrillary acidic protein (Gfap); apolipoprotein D (ApoD); ATPase, H⁺ transporting, V0 subunit B (Atp6vob). Relative amount of mRNA compared to young control is shown for each group. Lines above/below bars indicate standard error. C5: 5-month-old control diet; C30: 30-month-old control diet; α-T: 30-month-old α-tocopherol supplemented mice; α/γ-T: 30-month-old the mixture of α- and γ-tocopherol supplemented mice. * Significantly different from young control (p-value < 0.05). • Significantly different from old control (p-value < 0.05).