title: Prospective study of telomere length and LINE-1 methylation in peripheral blood cells: the role of B vitamins supplementation.
abstract: OBJECTIVE
  Deficiencies of folate, vitamins B12 and D are common age-related conditions. Vitamin B12 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 B12, B6, 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 B12, 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 < 12 µmol/L.
  
  
  CONCLUSIONS
  The results suggest a possible effect of B vitamins for telomere biology in blood cells. Suboptimal B vitamins status and hyperhomocysteinemia are associated with altered DNA methylation and telomere length. These data have to be confirmed in future studies.
authors: Department of Clinical Chemistry and Laboratory Medicine, Saarland University Hospital, 66421, Homburg/Saar, Germany.
authors: Irene
authors: I
authors: Pusceddu
authors: Department of Clinical Pathology, District Hospital Bolzano, Bolzano, Italy.
authors: Markus
authors: M
authors: Herrmann
authors: Department of Clinical Chemistry and Laboratory Medicine, Saarland University Hospital, 66421, Homburg/Saar, Germany.
authors: Susanne H
authors: SH
authors: Kirsch
authors: Department of Cardiology, Saarland University Hospital, Homburg/Saar, Germany.
authors: Christian
authors: C
authors: Werner
authors: Department of Clinical Chemistry and Laboratory Medicine, Saarland University Hospital, 66421, Homburg/Saar, Germany.
authors: Ulrich
authors: U
authors: Hübner
authors: Department of Clinical Chemistry and Laboratory Medicine, Saarland University Hospital, 66421, Homburg/Saar, Germany.
authors: Marion
authors: M
authors: Bodis
authors: Department of Cardiology, Saarland University Hospital, Homburg/Saar, Germany.
authors: Ulrich
authors: U
authors: Laufs
authors: Department of Biometry and Epidemiology, Saarland University Hospital, Homburg/Saar, Germany.
authors: Stefan
authors: S
authors: Wagenpfeil
authors: Department of Clinical Chemistry and Laboratory Medicine, Saarland University Hospital, 66421, Homburg/Saar, Germany.
authors: Jürgen
authors: J
authors: Geisel
authors: Department of Clinical Chemistry and Laboratory Medicine, Saarland University Hospital, 66421, Homburg/Saar, Germany. prof.wolfgang.herrmann@uniklinikum-saarland.de.
authors: Wolfgang
authors: W
authors: Herrmann
mesh_terms: D000368:Aged; D001773:Blood Cells / Q000187:drug effects*; D002118:Calcium / Q000008:administration & dosage / Q000097:blood; D003430:Cross-Sectional Studies; D019175:DNA Methylation / Q000187:drug effects*; D019587:Dietary Supplements; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000097:blood; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000188:drug therapy; D016014:Linear Models; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012435:S-Adenosylhomocysteine / Q000097:blood; D012436:S-Adenosylmethionine / Q000097:blood; D016615:Telomere / Q000648:ultrastructure*; D013763:Tetrahydrofolates / Q000097:blood; D014805:Vitamin B 12 / Q000008:administration & dosage / Q000097:blood; D025101:Vitamin B 6 / Q000008:administration & dosage / Q000097:blood; D014803:Vitamin B Complex / Q000008:administration & dosage* / Q000097:blood; D014807:Vitamin D / Q000008:administration & dosage / Q000097:blood
chemical_list: D013763:Tetrahydrofolates; D006710:Homocysteine; D014803:Vitamin B Complex; D014807:Vitamin D; D012436:S-Adenosylmethionine; D025101:Vitamin B 6; D005492:Folic Acid; D012435:S-Adenosylhomocysteine; D014805:Vitamin B 12; D002118:Calcium; C005984:5-methyltetrahydrofolate
keywords: B vitamins; DNA methylation; Telomere length