Effect of a High Folic Acid Diet on Telomere Length of Colonic Mucosa in Mice

In vitro studies and mathematical modeling suggest that excess folate can inhibit folate cycle and mimic folate deficiency. Under low folate conditions telomeres may shorten due to DNA damage or become abnormally long possibly due to loss of epigenetic control from DNA hypomethylation, both of which are associated with chromosomal instability. Our prior work has shown that high plasma folate is associated with shorter leukocyte telomere length in Framingham Offspring cohort. We investigated the effect of high folic acid diet on telomere length of colonic mucosa in mice. Young (3 months) and old mice (16 months) mice were fed a control (1xRDA) or high folic acid (20 x RDA) diet for 3 months (n=8‐10/ group). Folate was determined using a microbial assay and telomere length was determined using a real‐time PCR method as the ratio of telomeric repeats to a single copy gene. The data were analyzed using students t‐test. Both young and old mice on high folic acid diet had significantly higher folate in colonic mucosa compared to their respective controls (young 13.36 ± 3.6 vs 17.2± 2.7 ng folate/mg protein; p=0.01 and old 11.8 ± 2.1 vs 14.4 ± 2.1 ng folate/mg protein; p<0.01). The colonic mucosal telomere length of old mice were significantly shorter than that of the young mice (1.1 ± 0.4 vs 1.7 ± 0.56; p<0.01). High folic acid diet was associated with a non‐significant trend for shorter telomere length in young mice (1.27 ± 0.75 vs 1.7 ± 0.56; p=0.15) suggesting DNA damage. In old mice, telomere length was significantly longer in those on high folic acid diet when compared to those on control diet (1.73 ±0.6 vs 1.1 ± 0.4; p=0.01). Further research is needed to determine if this is due to loss of epigenetic control of telomere length. Support: HNRCA pilot grant, USDA 1950‐51000‐082‐00D