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

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Abstract

Purpose

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.

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Authors and Affiliations

  1. Department of Clinical Chemistry and Laboratory Medicine, Saarland University Hospital, 66421, Homburg/Saar, Germany

    Irene Pusceddu, Susanne H. Kirsch, Ulrich Hübner, Marion Bodis, Jürgen Geisel & Wolfgang Herrmann

  2. Department of Clinical Pathology, District Hospital Bolzano, Bolzano, Italy

    Markus Herrmann

  3. Department of Cardiology, Saarland University Hospital, Homburg/Saar, Germany

    Christian Werner & Ulrich Laufs

  4. Department of Biometry and Epidemiology, Saarland University Hospital, Homburg/Saar, Germany

    Stefan Wagenpfeil

Authors
  1. Irene Pusceddu
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  2. Markus Herrmann
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  3. Susanne H. Kirsch
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  4. Christian Werner
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  6. Marion Bodis
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Correspondence to Wolfgang Herrmann.

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Pusceddu, I., Herrmann, M., Kirsch, S.H. et al. Prospective study of telomere length and LINE-1 methylation in peripheral blood cells: the role of B vitamins supplementation. Eur J Nutr 55, 1863–1873 (2016). https://doi.org/10.1007/s00394-015-1003-1

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  • DOI: https://doi.org/10.1007/s00394-015-1003-1

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