Skip to main content
ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #240821
Title: Telomete length in peripheral blood mononuclear cells is associated with folate status in men

Author
item PAUL, LIGI - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item CATTANEO, MARCO - University Of Milano
item D'ANGELO, ARMANDO - San Raffaele Scientific Institute
item SAMPIETRO, FRANCESCA - San Raffaele Scientific Institute
item FERMO, ISABELLA - San Raffaele Scientific Institute
item RAZZARI, CRISTINA - University Of Milano
item FONTANA, GESSICA - University Of Milano
item EUGENE, NINDRA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item JACQUES, PAUL - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item SELHUB, JACOB - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/9/2009
Publication Date: 7/1/2009
Citation: Paul, L., Cattaneo, M., D'Angelo, A., Sampietro, F., Fermo, I., Razzari, C., Fontana, G., Eugene, N., Jacques, P.F., Selhub, J. 2009. Telomete length in peripheral blood mononuclear cells is associated with folate status in men. Journal of Nutrition. 139:1273-1278.

Interpretive Summary: The genetic material DNA is bound to proteins called histones and organised into structures called chromosomes. The ends of the chromosomes are protected by telomeres, which are repetitive DNA bound to specific proteins. The length of the telomeres is reduced with increasing cell divisions except when the enzyme telomerase is active as seen in stem cells and germ cells. Integrity of telomeric DNA and modifications to DNA or histones by addition of a chemical group (methyl group) in the telomeric region can determine the length as well as function of the telomere. Dysfunction of telomeres manifested as changes in telomere length is associated with many age-related pathologies including cancer, Alzheimer disease, Parkinson disease and cardiovascular disease. The B vitamin folate provides precursors for the components of DNA as well as provides methyl groups for modification of DNA. Reduced availability of folate results in loss of DNA integrity and reduced DNA methylation, which in turn influence telomere length. In this study we report that folate nutritional status was associated with telomere length in healthy men. There was a U-shaped relationship between plasma folate concentration and telomere length, with longer telomeres at the lowest and highest ends of folate status. A common variation in the DNA sequence for the gene methylene tetrahydrofolate reductase which has been implicated in increased cancer risk, was weakly associated with increased telomere length when folate nutrition is low. We propose that modulation of telomere integrity could be one of the mechanisms by which folate nutritional status affect disease risk.

Technical Abstract: Human chromosomes are capped by tandem repeats of DNA and associated proteins termed telomeres. The length of the telomeres is reduced with increasing cell divisions except when the enzyme telomerase is active as seen in stem cells and germ cells. Telomere dysfunction has been associated with development of age-related pathologies including cancer, cardiovascular disease, Alzheimer’s disease and Parkinson’s disease. DNA damage in telomeric region causes attrition of telomeres. Since folate provides precursors for nucleotide synthesis, thus affecting the integrity of DNA including that of the telomeric region, folate status has the potential to influence telomere length. Telomere length is epigenetically regulated by DNA methylation which in turn could be modulated by folate status. In this study we determined whether folate status and the 677C>T polymorphism of the methylene tetrahydrofolate reductase (MTHFR) gene are associated with the telomere length of peripheral blood mononuclear cells in healthy men. The results of our study showed that plasma concentration of folate was associated with telomere length of peripheral blood mononuclear cells in a non-linear manner. When plasma folate concentration was above the median, there was a positive relationship between folate and telomere length. In contrast, there was an inverse relationship between folate and telomere length when plasma folate concentration was below the median. The MTHFR 677C>T polymorphism was weakly associated (non- significant) with increased telomere length at below median folate status. We propose that folate status influences telomere length by affecting DNA integrity and the epigenetic regulation of telomere length through DNA methylation.