Prospective study of telomere length and LINE-1 methylation in peripheral blood cells: the role of B vitamins supplementation

• Published in: European journal of nutrition 2016-08, Vol.55 (5), p.1863-1873
• Main Authors: Pusceddu, Irene, Herrmann, Markus, Kirsch, Susanne H., Werner, Christian, Hübner, Ulrich, Bodis, Marion, Laufs, Ulrich, Wagenpfeil, Stefan, Geisel, Jürgen, Herrmann, Wolfgang
• Format: Article
• Language: English
• Subjects: Aged; Blood Cells - drug effects; Calcium - administration & dosage; Calcium - blood; Chemistry; Chemistry and Materials Science; Cross-Sectional Studies; Dietary Supplements; DNA Methylation - drug effects; Female; Folic Acid - administration & dosage; Folic Acid - blood; Homocysteine - blood; Humans; Hyperhomocysteinemia - drug therapy; Linear Models; Long Interspersed Nucleotide Elements - genetics; Male; Middle Aged; Nutrition; Original Contribution; Prospective Studies; S-Adenosylhomocysteine - blood; S-Adenosylmethionine - blood; Telomere - ultrastructure; Tetrahydrofolates - blood; Vitamin B 12 - administration & dosage; Vitamin B 12 - blood; Vitamin B 6 - administration & dosage; Vitamin B 6 - blood; Vitamin B Complex - administration & dosage; Vitamin B Complex - blood; Vitamin D - administration & dosage; Vitamin D - blood
• ISSN: 1436-6207; 1436-6215
• DOI: 10.1007/s00394-015-1003-1

Purpose Deficiencies of folate, vitamins B 12 and D are common age-related conditions. Vitamin B 12 and folate are necessary for DNA methylation. Telomeres appear to be regulated by DNA methylation. Here, we study the effect of B vitamins supplementation on telomere length and global DNA methylation in a prospective study. Methods In total, 60 elderly subjects were supplemented for 1 year with either vitamin B 12 , B 6 , folate, vitamin D and calcium (group A n  = 31) or only vitamin D and calcium (group B n  = 29). LINE-1 methylation, relative telomere length (T/S), vitamin B 12 , folate, homocysteine (tHcy) , 5-methyltetrahydrofolate (5-methylTHF), S -adenosylhomocysteine (SAH), S -adenosylmethionine (SAM), cystathionine and vitamin D were quantified before and after supplementation. Results At baseline, tHcy was high, vitamin D was low, and T/S did not differ between groups A and B. Vitamin supplementation increased LINE-1 methylation in group A at site 317 but reduced LINE-1 methylation in group B at site 327. There was no correlation between T/S and LINE-1 methylation at baseline. Multiple backward regression analysis revealed baseline tHcy and 5-methylTHF are significant predictors of T/S. After supplementation in group B but not in group A, LINE-1 methylation correlated inversely with T/S, and LINE-1 methylation variation was an independent predictor of T/S variation. B vitamins decreased tHcy significantly in group A. Multiple backward regression analysis showed 5-methylTHF in group A and tHcy in group B were significant predictors for LINE-1 methylation. At baseline, the lower LINE-1 methylation observed in subjects with 5-methylTHF >10 nmol/l was in agreement with a reduced methyl group transfer due to a lower SAM formation. In group B, an increase in telomere length was correlated with lower LINE-1 methylation. Subjects with hyperhomocysteinemia >12 µmol/L had compared to those with normal tHcy a reduced LINE-1 methylation accompanied by a higher SAM and SAH (that inhibits demethylation of SAM) as well as lower 5-methylTHF. Additionally, subjects with tHcy > 12 µmol/L had longer telomeres when compared with subjects having tHcy