Genomic DNA methylation decreases in response to moderate folate depletion in elderly women.
BACKGROUND
Methylation of genomic DNA is dependent on an adequate supply of folate coenzymes. Previous data support the hypothesis that abnormal DNA methylation plays an integral role in carcinogenesis. To date, no studies assessing the effect of inadequate folate status on DNA methylation in older women (aged >63 y) have been reported.


OBJECTIVE
The effect of moderate folate depletion followed by folate repletion on leukocyte genomic DNA methylation was investigated in elderly women (aged 60-85 y) to evaluate whether DNA methylation could be used as a functional indicator of folate status.


METHODS
Healthy, postmenopausal women (n = 33) consumed a moderately folate-depleted diet (118 microg folate/d) for 7 wk, followed by 7 wk of folate repletion with 200 or 415 microg/d, each provided as 2 different dietary treatments for a total of 4 treatment groups (n = 30). Leukocyte DNA methylation was determined on the basis of the ability of DNA to incorporate [(3)H]methyl groups from labeled S:-adenosylmethionine in an in vitro assay.


RESULTS
Incorporation of [(3)H]methyl groups increased significantly (P: = 0.0025) in response to folate depletion, suggesting undermethylation of DNA. No significant changes were detected in [(3)H]methyl incorporation in any group over the 7-wk repletion period compared with postdepletion values.


CONCLUSIONS
DNA methylation status may be used as a functional indicator of moderately depleted folate status. The slow response to the repletion diets observed suggests that normalization of DNA methylation after moderate folate depletion may be delayed in older women.
Rampersaud
G C
GC
Food Science and Human Nutrition Department, College of Agricultural and Life Sciences, Gainesville, FL, USA.
Kauwell
G P
GP
Hutson
A D
AD
Cerda
J J
JJ
Bailey
L B
LB
D000368:Aged; D000369:Aged, 80 and over; D004247:DNA / Q000737:chemistry / Q000302:isolation & purification; D019175:DNA Methylation; D015257:DNA-Cytosine Methylases / Q000737:chemistry; D019587:Dietary Supplements; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage* / Q000097:blood; D005494:Folic Acid Deficiency / Q000097:blood / Q000178:diet therapy*; D006710:Homocysteine / Q000097:blood; D006801:Humans; D016018:Least-Squares Analysis; D007962:Leukocytes / Q000737:chemistry; D008875:Middle Aged; D018673:Nutrition Policy; D012436:S-Adenosylmethionine / Q000737:chemistry; D012588:Scintillation Counting; D018709:Statistics, Nonparametric
D006710:Homocysteine; D012436:S-Adenosylmethionine; D004247:DNA; D005492:Folic Acid; C081573:DNA modification methylase SssI; D015257:DNA-Cytosine Methylases