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United States Department of Agriculture

Agricultural Research Service

Research Project: ONE-CARBON NUTRIENTS IN THE PREVENTION OF CANCER

Location: Human Nutrition Research Center on Aging

Title: Aging is a more significant determinant of hepatic DNA methylation patterns than a western style diet

Authors
item Park, Lara -
item Saltzman, Edward -
item Schnitzler, Gavin -
item Yoon, Byung Woo -
item PARNELL, LAURENCE
item LAI, CHAO QIANG
item Choi, San Woon -

Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Abstract Only
Publication Acceptance Date: March 29, 2012
Publication Date: March 29, 2012
Citation: Park, L.K., Saltzman, E., Schnitzler, G., Yoon, B., Parnell, L.D., Lai, C., Choi, S. 2012. Aging is a more significant determinant of hepatic DNA methylation patterns than a western style diet. Journal of Federation of American Societies for Experimental Biology. 2012(26):243.5.

Technical Abstract: We investigated how DNA methylation patterns change with aging and a Western style diet (WSD) in the liver. 2-month old male C57BL/6 mice were randomized to control diet (CD) or WSD for either the following 6 (young) or 18 months (old). WSD is high in fat and low in fiber, vitamins and minerals. Methylation was investigated by the methylated DNA immunoprecipitation-chip method on arrays covering all RefSeq genes and CpG islands. Modified t-tests with the Benjamini-Hochberg (BH) correction for multiple comparisons (a=0.05) were performed per probe for age and diet contrasts. Within n=713,168 probes, we found 17.0% and 8.7 % significant probes by age within CD and WSD, respectively. Ingenuity Pathway Analysis identified similar patterns by aging in WSD and CD with enrichment of genes in cancer, lipid metabolism, epigenetic regulation and neural function. Specifically, we observed hypermethylation of the Jumonji subunit Kdm6b and hypomethylation of Ras member Rap2a, cholesterol metabolism enzyme Hsd3b5, mitochondrial metabolism enzyme Suclg1 and multiple olfactory and vomeronasal receptors. No significant probes passed BH when comparing diets at the same age. Thus, aging has a greater effect than diet on hepatic DNA methylation patterns with enrichment of genes that may potentiate chronic disease development. Gene expression remains to be evaluated. Supported by NIH Grants R01 AG25834.

Last Modified: 8/19/2014
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