Effect of High Folic Acid Diet on Mitochondrial DNA Content in Young Adult and Aged Mice

Abstract

Mitochondrial DNA (mtDNA) codes for proteins of oxidative phosphorylation system and maintaining adequate mtDNA copy number is necessary for cell survival. Studies in animal models have shown that folate deficiency can affect mtDNA content. Current data suggests excess folic acid intake can result in conditions that resemble folate deficiency. We tested the hypothesis that excess folic acid in diet can influence mtDNA gene content in old and young 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=8–11/ group). The colonic mucosal mtDNA content was determined by real‐time PCR using primers specific for mtDNA and normalized to an endogenous reference gene, mapK. The data were analyzed using student's t‐test. Among mice on control diet, mtDNA content of old mice was 0.4 fold that of the young mice (p=0.004). There was no difference in mtDNA content of young mice on control vs high folic acid diet. MtDNA content of the old mice fed a high folic acid diet was 7‐fold higher than those fed a control diet (p=0.001). While higher mtDNA copy number is considered to have beneficial effects on survival, very high mtDNA copy number has been shown to be accompanied by nucleoid enlargement, defective transcription and mtDNA deletions in old mice. Thus the dramatic increase in mtDNA content due to excess folic acid diet may be detrimental. Further research is required to establish if the high mtDNA content due a high folic acid diet can result in mitochondrial dysfunction in aged mice.Support or Funding InformationSupport from USDA cooperative agreement 51520‐008‐04S and pilot grant from JM USDA HNRCA on Aging at Tufts University