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A western style diet reduces genomic DNA methylation and aging increases p16 promoter DNA methylation in mouse colon
Author(s) -
Tammen Stephanie,
Zimmerly Ella,
Ledbetter Sarah,
Park Lara K,
Choi SangWoon
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.598.3
Subject(s) - dna methylation , methylation , epigenetics , genomic dna , carcinogenesis , biology , promoter , methylated dna immunoprecipitation , microbiology and biotechnology , dna , genetics , gene expression , gene
A mouse model consuming a western style diet (WSD) which is high in fat and calories and low in calcium, vitamin D, fiber, methionine and choline is known to develop colonic tumors. We investigated the epigenetic effects of a WSD on genomic and p16 promoter DNA methylation, both of which are known to be altered in cancer and aging. Forty‐six mice were fed either a WSD or a control diet (AIN76A) and killed after 6, 12 or 18 months on the diet. Genomic DNA methylation, p16 promoter methylation and p16 expression were determined by LC/MS, methyl specific PCR and real time RT‐PCR, respectively. The WSD group demonstrated significantly decreased genomic DNA methylation compared with the control at 6 months (4.08 vs 4.32%, p<0.05) and 18 months (4.09 vs 4.31%, p<0.01). Neither diet group showed a significant difference in genomic DNA methylation over time. There was an increase in p16 promoter methylation from 6 to 18 months in both diet groups (p<0.05) but no differences were observed between diet groups. Compared with 6 months, WSD and control showed a significantly reduced p16 expression at 18 months and 12 months, respectively (p<0.05). In this model WSD reduces genomic DNA methylation while aging increases p16 promoter methylation and decreases p16 expression, which are all common epigenetic features in colonic carcinogenesis. Grant Funding Source : NIH Grants R01 AG25834 and USDA agreement #58‐1950‐7‐707