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Aging increases genomic DNA methylation in the colonic mucosa of the mouse
Author(s) -
Keyes Mary Katharine,
Jang Hyeran,
Dolnikowski Gregory,
Liu Zhenhua,
Mason Joel B,
Choi SangWoon
Publication year - 2006
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.20.4.a602-c
Subject(s) - dna methylation , methylation , epigenetics , genomic dna , dna , microbiology and biotechnology , cytosine , biology , endocrinology , gene , medicine , gene expression , andrology , biochemistry
In human studies, advanced age and decreased folate status have each been identified as determinants of DNA methylation, an epigenetic phenomenon related to gene expression and integrity. Nevertheless, previous research which examined middle‐aged laboratory rodents failed to show a change in DNA methylation status related to age. We therefore investigated the effects of these modifying factors on genomic DNA methylation in the colonic mucosa of young and genuinely aged mice. Young (4 mo) male C57BL/6 mice (n=32) and old (18 mo) mice (n=28) were divided into three groups, and fed diets containing 0, 2 or 8mg folic acid/kg (deplete, replete and supplemented groups, respectively) for 20 weeks. Plasma folate concentration and colonic genomic DNA methylation were measured by radioimmunoassay and LC/MS, respectively. Plasma folate concentrations increased with dietary folate levels in both young and old mice in a dose‐dependent fashion (P< 0.002). The old mice had significantly higher DNA methylation than the young in each diet group (5.99±0.47, 5.34±0.71, and 5.93±0.48 vs. 4.45±0.52, 4.76±0.27, and 4.95±0.25 % of methylcytosine in total cytosine residues, folate‐deplete, ‐replete and –supplemented, respectively p<0.05). In young mice, genomic DNA methylation increased in a manner that was directly dependent on dietary folate (p for trend <0.01). This pattern was not evident in the old mice. In conclusion, in the colon of the old mouse, genomic DNA methylation is uniformly increased compared to that of the young, and it loses its dependence on dietary folate status.