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Supplementation Of Selenium-enriched Yeast Attenuates Age-dependent Transcriptional Changes Of Heart In Mitochondrial DNA Mutator Mice

Rijin Xiao, Leya Spangler, Katie Routt, Zijian Lan, Carrie Johnson, Tomas A Prolla, Ronan F Power

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Background: Age is a major risk factor in developing heart diseases and has been associated with profound transcriptional changes in mammalian tissues. Low tissue selenium has recently been linked to several age-related diseases, including cardiovascular disease. This study investigated the global effects of age and dietary supplementation of selenium on heart transcriptional profiles in POLG mutator mice.Methods: Heart transcription profiles from young (2-month-old) and old (13-month-old) animals fed either a control diet or a diet supplemented with 1.0 mg selenium from selenium-enriched yeast (SP)/kg diet were obtained and validated using microarray and real-time RT-PCR techniques.Results: Aging led to significant transcriptional changes, where the expression of 1942 genes in old animals was changed by a fold change larger than 2.0, when compared to young animals. Age-regulated genes are associated with cardiovascular system development, immune and inflammatory response, and cellular oxidative stress response. Multiple genes linked with cardiomyocyte apoptosis, hypertrophy, and cardiac fibrosis, such as Myh7, Lcn2, Spp1, and Serpine1, were significantly up-regulated in old animals. SP supplementation also caused significant transcriptional changes in the heart, especially in old mice where many age-dependent transcriptional changes were totally or partially reversed by SP. Upstream regulator analysis further indicated that genes for Foxo1 and Foxo3, two transcriptional regulators involved in the regulation of cardiac muscle remodeling, were significantly activated by SP, suggesting that Foxo-mediated transcriptional activities play important roles in the anti-aging properties of SP.Conclusions: Results of this study indicate that SP supplementation attenuated age-related transcriptional changes in the heart of old POLG mice, which implies a potential clinical application of dietary selenium in preventing decline of cardiac function in old animals.  Key words: Aging, heart, gene expression, selenium