Aging and alcohol interact to alter hepatic DNA hydroxymethylation

Area of Science:

• Epigenetics
• Molecular Biology
• Gerontology

Background:

• DNA methylation and chronic alcohol consumption are known to modify DNA methylation.
• DNA hydroxymethylation, an epigenetic mark derived from methylcytosine oxidation, is newly discovered.
• The interaction between aging and alcohol on DNA hydroxymethylation and its effect on gene expression remains unexplored.

Purpose of the Study:

• To investigate the impact of chronic alcohol consumption on DNA hydroxymethylation.
• To determine if aging and alcohol consumption interact to modify DNA hydroxymethylation.
• To explore the potential effects of these modifications on gene expression.

Main Methods:

• Utilized a mouse model comparing young (4 months) and old (18 months) male C57BL/6 mice.
• Mice were fed either an alcohol-containing or control liquid diet for 5 weeks.
• Analyzed global DNA hydroxymethylation and methylation in liver tissue using liquid chromatography-tandem mass spectrometry and measured Tet enzyme mRNA expression via quantitative real-time polymerase chain reaction.

Main Results:

• Chronic alcohol consumption significantly reduced DNA hydroxymethylation in young mice.
• Alcohol did not significantly alter hydroxymethylation levels in old mice.
• A significant interaction between aging and alcohol consumption was observed in determining DNA hydroxymethylation levels, with decreased Tet2 and Tet3 expression in older mice.

Conclusions:

• Chronic alcohol consumption represents a novel epigenetic influence on DNA hydroxymethylation.
• This study provides the first evidence of interactive effects between chronic alcohol consumption and aging on DNA hydroxymethylation.