High plasma folate is negatively associated with leukocyte telomere length in Framingham Offspring cohort

Abstract

Purpose Shortening of telomeres, the protective structures at the ends of eukaryotic chromosomes, is associated with age-related pathologies. Telomere length is influenced by DNA integrity and DNA and histone methylation. Folate plays a role in providing precursors for nucleotides and methyl groups for methylation reactions and has the potential to influence telomere length. Method We determined the association between leukocyte telomere length and long-term plasma folate status (mean of 4 years) in Framingham Offspring Study (n=1044, female =52.1%, mean age 59 y) using data from samples collected before and after folic acid fortification. Leukocyte telomere length was determined by Southern analysis and fasting plasma folate concentration using microbiological assay. Results There was no significant positive association between long-term plasma folate and leukocyte telomere length among the Framingham Offspring Study participants perhaps due to their adequate folate status. While the leukocyte telomere length in the second quintile of plasma folate was longer than that of the first quintile, the difference was not statistically significant. The leukocyte telomere length of the individuals in the fifth quintile of plasma folate was shorter than that of those in the second quintile by 180 bp (P<0.01). There was a linear decrease in leukocyte telomere length with higher plasma folate concentrations in the upper 4 quintiles of plasma folate (P for trend =0.001). Multivitamin use was associated with shorter telomeres in this cohort (P=0.015). Conclusions High plasma folate status possibly resulting from high folic acid intake may interfere with the role of folate in maintaining telomere integrity.

Increased Telomere Attrition After Renal Transplantation—Impact of Antimetabolite Therapy

“…17,19,21,23 However, it has also been reported that elevated folate stimulates cell division, 45 which could increase telomere attrition through its involvement in nucleotide synthesis. Indeed, Paul et al 46 have reported decreasing telomere length with increasing folate, and a recent study has shown that folate deficiency results in telomere elongation. 47 Because telomere length is inversely associated with plasma homocysteine, this suggests that it may be an intermediary in the relationship between homocysteine and CVD.…”

Telomeres, Aging, and Nutrition

“…Multivitamin use was associated with shorter telomeres in this cohort (P 5 0.015) [69] 586 participants (age 35À74 years) in the Sister Study (USA)…”

“…[69] 786 participants in the Austrian Stroke Prevention Study 9 mean age of 66 6 7 58% female) There was a linear decrease in leukocyte telomere length with higher plasma folate concentrations in the upper four quintiles of plasma folate (P for trend 5 0.001).…”

“…Higher intake of processed meat, red meat, sweetened carbonated beverages, white bread, short-to medium-chain saturated fatty acids and their sources such as whole milk (and products such as butter and cheese), linoleic acid (n6 fatty acid), and higher sodium intake (in those with high BMI) were all associated with shorter telomeres [58,59,65,67,68,70,71]. Multivitamin use was associated with both shorter and longer telomeres [69,70].…”

“…Studies on blood nutrient concentrations showed U-shaped relationships between plasma folate and telomere length [69,75] and a reduction of telomere length is associated with higher homocysteine (a metabolic biomarker of folate and/or vitamin B12 deficiency) in older subjects indicating a rather complex relationship with B vitamins [72À74]. Higher plasma zeaxanthin, lutein, vitamin C, vitamin D, and Ca/Mg ratio was associated with longer telomeres but, in contrast, higher plasma concentration of calcium, magnesium, and zinc was associated with shorter telomeres (the latter in children) [76À79].…”