title: A lifelong exposure to a Western-style diet, but not aging, alters global DNA methylation in mouse colon.
abstract: OBJECTIVE
  Previous studies have indicated that when compared to young mice, old mice have lower global DNA methylation and higher p16 promoter methylation in colonic mucosa, which is a common finding in colon cancer. It is also known that a Western-style diet (WSD) high in fat and calories, and low in calcium, vitamin D, fiber, methionine and choline (based on the AIN 76A diet) is tumorigenic in colons of mice. Because DNA methylation is modifiable by diet, we investigate whether a WSD disrupts DNA methylation patterns, creating a tumorigenic environment.
  We investigated the effects of a WSD and aging on global and p16 promoter DNA methylation in the colon. Two month old male C57BL/6 mice were fed either a WSD or a control diet (AIN76A) for 6, 12 or 17 months. Global DNA methylation, p16 promoter methylation and p16 expression were determined by LC/MS, methyl-specific PCR and real time RT-PCR, respectively.
  
  
  RESULTS
  The WSD group demonstrated significantly decreased global DNA methylation compared with the control at 17 months (4.05 vs 4.31%, P = 0.019). While both diets did not change global DNA methylation over time, mice fed the WSD had lower global methylation relative to controls when comparing all animals (4.13 vs 4.30%, P = 0.0005). There was an increase in p16 promoter methylation from 6 to 17 months in both diet groups (P < 0.05) but no differences were observed between diet groups. Expression of p16 increased with age in both control and WSD groups.
  
  
  CONCLUSIONS
  In this model a WSD reduces global DNA methylation, whereas aging itself has no affect. Although the epigenetic effect of aging was not strong enough to alter global DNA methylation, changes in promoter-specific methylation and gene expression occurred with aging regardless of diet, demonstrating the complexity of epigenetic patterns.
authors.affiliation: Chaum Life Center, CHA University School of Medicine, 442, Dosan-daero, Gangnam-gu, Seoul 135-948, Korea. ; Friedman School of Nutrition Science and Policy Tufts University, Boston, Massachusetts, USA. ; School of Public Health and Health Sciences, University of Massachusetts, Amherst, Massachusetts, USA.
authors.forename: Sang-Woon
authors.initials: SW
authors.lastname: Choi
authors.affiliation: Friedman School of Nutrition Science and Policy Tufts University, Boston, Massachusetts, USA.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Tammen
authors.affiliation: School of Public Health and Health Sciences, University of Massachusetts, Amherst, Massachusetts, USA.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Liu
authors.affiliation: University of Verona School of Medicine, Verona, Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Friso
keywords: DNA methylation; Western-style diet; aging; colon; mouse