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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #173375
Title: FOLATE SUPPLEMENTATION INCREASES GENOMIC DNA METHYLATION OF THE LUNG IN YOUNG, BUT NOT IN OLD MICE

Author
item JANG, HYERAN - TUFTS UNIVERSITY
item KEYES, MARY - TUFTS/HNRCA
item Dolnikowski, Gregory
item LIU, ZHENHUA - TUFTS/HNRCA
item CROTT, JIMMY - TUFTS/HNRCA
item Mason, Joel
item Choi, Sang-Woon

Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Abstract Only
Publication Acceptance Date: 11/3/2004
Publication Date: 4/1/2005
Citation: Jang, H., Keyes, M.K., Dolnikowski, G., Liu, Z., Crott, J.W., Mason, J.B., Choi, S. 2005. Folate supplementation increases genomic DNA methylation of the lung in young, but not in old mice [abstract]. Journal of Federation of American Societies for Experimental Biology. Paper No. 161.4.

Interpretive Summary:

Technical Abstract: Aging and folate depletion are each considered to be risk factors for lung cancer. We therefore examined whether interactions between aging and folate status impact on onecarbon metabolism, using genomic DNA methylation and uracil misincorporation into DNA as cancer-relevant endpoints. Young (weanling) male C57BL/6 mice (n=32) and old (18 month) mice (n=34) were each 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, lung genomic DNA methylation and lung DNA uracil misincorporation were measured by radioimmunoassay, LC/MS and GC/MS, respectively. Plasma folate concentrations increased with dietary folate levels in both young and old mice in a dose-dependent fashion. Folate depletion did not diminish genomic DNA methylation in either age group. Young mice fed the folate supplemented diet had a significantly higher amount of DNA methylation than both young-replete and old-supplemented mice (3.6±1.2 vs 2.4±0.7 and 2.3±1.0ng methylcytosine/ug DNA, respectively, P<0.05). Neither age nor dietary folate levels affected uracil misincorporation into lung DNA. In conclusion, old mice display a resistance to an elevation in lung genomic DNA methylation that is otherwise observed in young with folate supplementation.