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One‐carbon metabolism in the aged colon after folic acid supplementation
Author(s) -
Zimmerly Ella M,
Kim KyongChol,
Jang Hyeran,
Choi SangWoon
Publication year - 2010
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.24.1_supplement.738.10
Subject(s) - methylenetetrahydrofolate reductase , thymidylate synthase , metabolism , endocrinology , medicine , colorectal cancer , folic acid , chemistry , biology , biochemistry , cancer , gene , allele , fluorouracil
Age and low folate intake have been associated with increased risk of colorectal cancer, but excessive folate intake might increase this risk in the elderly. The polymorphism of methylenetetrahydrofolate reductase ( MTHFR ), a gene whose product determines folate utilization in one‐carbon metabolism, is also associated with the risk of colorectal cancer. In this study we examined changes in one‐carbon metabolism due to aging and folate intake. To mimic folate deplete, replete, and supplemented diets, young and old mice were fed 0, 2, or 8 mg folic acid/kg diet (AIN‐93M) for twenty weeks. In the colonic mucosa we examined relative gene expression of enzymes related to folate and thymidine handling using real time RT‐PCR. While old mice did not show changes, MTHFR expression decreased in young mouse colon with increased folic acid intake (p trend =0.038). Expression of thymidylate synthase (p=0.031) and deoxythymydylate synthase (p=0.025) was higher in older mice than in young but comparable among different diet groups. Thymidine kinase, dihydrofolate reductase, and serine hydroxymethyl transferase did not demonstrate differences by age or diet. Overall folic acid supplementation did not induce aberrant expression of one‐carbon metabolism genes in the colon of old mice. Supported by the NIH Grant R01 AG25834 Grant Funding Source : NIH