Submitted to: Journal of Nutritional Biochemistry
Publication Type: Review article
Publication Acceptance Date: 4/20/2009
Publication Date: 12/20/2009
Citation: Kim, K., Friso, S., Choi, S. 2009. DNA methylation, an epigenetic mechanism connecting folate to healthy embryonic development and aging. Journal of Nutritional Biochemistry. 20(12):917-926. Interpretive Summary:
Technical Abstract: Experimental studies demonstrated that maternal environmental factors including diet during early embryonic development can influence the phenotype of offspring as well as the risk of disease development at the later life. DNA methylation, an epigenetic phenomenon, has been suggested as a mechanism by which maternal nutrients affect the phenotype of their offspring in both honeybee and agouti mouse models. Phenotypic changes through DNA methylation can be linked to folate metabolism by the knowledge that folate, a coenzyme of one-carbon metabolism, is directly involved in methyl group transfer to DNA methylation. During the fetal period organ-specific DNA methylation patterns are established through epigenetic reprogramming. However, established DNA methylation patterns are not immutable and can be changed during our life time by environment. Aberrant changes in DNA methylation by diet may lead to the development of age-associated diseases including cancer. It is also known that the aging process by itself is accompanied by alterations in DNA methylation. Diminished activity of DNA methyltransferase (Dnmt) can be a potential mechanism for decreased genomic DNA methylation during aging, along with reduced intake of folate and altered folate metabolism. Progressive hypermethylation in the promoter of certain genes was found with aging and repression of tumor suppressors by this epigenetic mechanism appears to be associated with cancer. In this review we address the effect of folate on early development and aging through an epigenetic mechanism, DNA methylation.