title: Aging and alcohol interact to alter hepatic DNA hydroxymethylation.
abstract: BACKGROUND
  Aging and chronic alcohol consumption are both modifiers of DNA methylation, but it is not yet known whether chronic alcohol consumption also alters DNA hydroxymethylation, a newly discovered epigenetic mark produced by oxidation of methylcytosine. Furthermore, it has not been tested whether aging and alcohol interact to modify this epigenetic phenomenon, thereby having an independent effect on gene expression.
  
  
  METHODS
  Old (18 months) and young (4 months) male C57BL/6 mice were pair-fed either a Lieber-DeCarli liquid diet with alcohol (18% of energy) or an isocaloric Lieber-DeCarli control diet for 5 weeks. Global DNA hydroxymethylation and DNA methylation were analyzed from hepatic DNA using a new liquid chromatography-tandem mass spectrometry method. Hepatic mRNA expression of the Tet enzymes were measured via quantitative real-time polymerase chain reaction.
  
  
  RESULTS
  In young mice, mild chronic alcohol exposure significantly reduced global DNA hydroxymethylation compared with control mice (0.22 ± 0.01 vs. 0.29 ± 0.06%, p = 0.004). Alcohol did not significantly alter hydroxymethylcytosine levels in old mice. Old mice fed the control diet showed decreased global DNA hydroxymethylation compared with young mice fed the control diet (0.24 ± 0.02 vs. 0.29 ± 0.06%, p = 0.04). This model suggests an interaction between aging and alcohol in determining DNA hydroxymethylation (pinteraction  = 0.009). Expression of Tet2 and Tet3 was decreased in the old mice relative to the young (p < 0.005).
  
  
  CONCLUSIONS
  The observation that alcohol alters DNA hydroxymethylation indicates a new epigenetic effect of alcohol. This is the first study demonstrating the interactive effects of chronic alcohol consumption and aging on DNA hydroxymethylation.
authors: Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts; Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts.
authors: Stephanie A
authors: SA
authors: Tammen
authors: Gregory G
authors: GG
authors: Dolnikowski
authors: Lynne M
authors: LM
authors: Ausman
authors: Zhenhua
authors: Z
authors: Liu
authors: Julia
authors: J
authors: Sauer
authors: Simonetta
authors: S
authors: Friso
authors: Sang-Woon
authors: SW
authors: Choi
mesh_terms: D000375:Aging / Q000235:genetics*; D000428:Alcohol Drinking / Q000235:genetics*; D000818:Animals; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis; D019175:DNA Methylation / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D049308:Dioxygenases; D044127:Epigenesis, Genetic / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D000431:Ethanol; D049308:Dioxygenases; C551914:Tet2 protein, mouse; C551915:Tet3 protein, mouse; D019392:Cytochrome P-450 CYP2E1
keywords: Aging; Alcohol; DNA Hydroxymethylation; Liver; Mouse