title: 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.
authors.affiliation: Department of Genetics and Medical Genetics, University of Wisconsin, Madison, WI 53706, USA.
authors.forename: Sang-Kyu
authors.initials: SK
authors.lastname: Park
authors.forename: Grier P
authors.initials: GP
authors.lastname: Page
authors.forename: Kyoungmi
authors.initials: K
authors.lastname: Kim
authors.forename: David B
authors.initials: DB
authors.lastname: Allison
authors.forename: Mohsen
authors.initials: M
authors.lastname: Meydani
authors.forename: Richard
authors.initials: R
authors.lastname: Weindruch
authors.forename: Tomas A
authors.initials: TA
authors.lastname: Prolla
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D001921:Brain / Q000502:physiology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D019587:Dietary Supplements; D004359:Drug Therapy, Combination; D020869:Gene Expression Profiling; D006321:Heart / Q000502:physiology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013047:Specific Pathogen-Free Organisms; D014158:Transcription, Genetic / Q000187:drug effects*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000494:pharmacology*; D024504:gamma-Tocopherol / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D016207:Cytokines; D016159:Tumor Suppressor Protein p53; D024504:gamma-Tocopherol; C092073:cardiotrophin 1; D024502:alpha-Tocopherol