title: Genetic and epigenetic interactions between folate and aging in carcinogenesis.
abstract: Folate is among the most strongly implicated dietary components to convey protection against colon cancer, and diminished folate status is associated with an enhanced risk of colon cancer. Age is also regarded as one of the most important risk factors for colonic carcinogenesis. It is therefore of considerable interest to determine whether the process of aging influences folate metabolism in the colon and whether folate supplementation might prevent the procarcinogenic effects associated with aging. Recent studies in our laboratory demonstrated that the colonic mucosa of elder rats is more susceptible to folate depletion than that of young rats. Depletion of folate results in a shift in the forms of folate in the colon as well as increased uracil incorporation into DNA, a purported mechanism for colonic carcinogenesis. However, modest folate supplementation eliminates evidence of inadequate folate status in the colons of elder rats, suggesting that the relation between age and folate status in the colon might be one mechanism by which aging modulates colorectal cancer risk. Interactions between folate and aging also affect a spectrum of epigenetic and genetic phenomena such as uracil misincorporation, DNA methylation, protein methylation, mitochondrial deletion, and critical gene expression, which could be related to carcinogenesis. Aging and inadequate dietary folate may interact and collectively induce derangements in folate metabolism, thereby provoking subsequent molecular aberrations, which may enhance carcinogenesis. However, folate supplementation appears to reverse these adverse effects of aging, which is potentially of substantial import because the latter is an unmodifiable risk factor.
authors.affiliation: Vitamins and Carcinogenesis Laboratory, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA.
authors.forename: Hyeran
authors.initials: H
authors.lastname: Jang
authors.forename: Joel B
authors.initials: JB
authors.lastname: Mason
authors.forename: Sang-Woon
authors.initials: SW
authors.lastname: Choi
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D019175:DNA Methylation; D044127:Epigenesis, Genetic / Q000502:physiology*; D005492:Folic Acid / Q000378:metabolism / Q000502:physiology*; D009369:Neoplasms / Q000209:etiology* / Q000235:genetics; D051381:Rats
chemical_list: D005492:Folic Acid