Clin Nutr Res.  2016 Jan;5(1):7-14. 10.7762/cnr.2016.5.1.7.

Leukocyte Telomere Length is Associated With Serum Vitamin B12 and Homocysteine Levels in Older Adults With the Presence of Systemic Inflammation

Affiliations
  • 1Department of Internal Medicine, Korea University Ansan Hospital, Ansan, 15355 Korea.
  • 2Department of Foods and Nutrition, College of Natural Sciences, Kookmin University, Seoul, 02707 Korea. ibaik@kookmin.ac.kr

Abstract

Folate, vitamin B12, and homocysteine (HCY) are involved in the metabolism of nucleic acid precursors and it has been hypothesized that they also influence telomere length, a biomarker of aging. However, previous studies have reported inconsistent findings, and data for older adults are limited. Our study aimed to evaluate associations between leukocyte telomere length (LTL) and serum folate, vitamin B12, and HCY levels among adults aged 55 years and over. In a cross-sectional study in 798 men and women aged 55-79 years, serum folate, vitamin B12, and HCY levels were measured using chemiluminescent immunometric assays, and relative LTL was assessed using quantitative real-time polymerase chain reaction. To evaluate associations between LTL and serum folate, vitamin B12, and HCY levels, multiple linear regression models were used. In multiple models adjusted for age, sex, serum high sensitive C-reactive protein (hs-CRP) levels, and other potential confounding factors, we found no association between LTL and serum folate, vitamin B12, and HCY levels. However, we did find a significant inverse association between HCY levels and LTL in participants with serum hs-CRP levels of > or = 2 mg/L (p < 0.05). Moreover, there was a trend toward an association between HCY and vitamin B12 levels in these individuals (p = 0.08). In those with serum hs-CRP levels of < 2 mg/L, HCY was inversely associated with vitamin B12 levels (p < 0.001) and had no association with LTL. Our findings suggest that increased serum HCY levels, when combined with the presence of systemic inflammation, may play a role in accelerating biological aging.

Keyword

Telomere length; B vitamins; Homocysteine; C-reactive protein; Older adults

MeSH Terms

Adult*
Aging
C-Reactive Protein
Cross-Sectional Studies
Female
Folic Acid
Homocysteine*
Humans
Inflammation*
Leukocytes*
Linear Models
Male
Metabolism
Nucleic Acid Precursors
Real-Time Polymerase Chain Reaction
Telomere*
Vitamin B 12*
Vitamin B Complex
Vitamins*
C-Reactive Protein
Folic Acid
Homocysteine
Nucleic Acid Precursors
Vitamin B 12
Vitamin B Complex
Vitamins

Figure

  • Figure 1 Prevalence of low, normal, or high levels of serum folate, vitamin B12, and homocysteine.


Reference

1. Mason JB. Biomarkers of nutrient exposure and status in one-carbon (methyl) metabolism. J Nutr. 2003; 133:Suppl 3. 941S–947S.
Article
2. Arinze IJ. Facilitating understanding of the purine nucleotide cycle and the one-carbon pool: Part I: The purine nucleotide cycle. Biochem Mol Biol Educ. 2005; 33:165–168.
Article
3. Fenech M. Folate (vitamin B9) and vitamin B12 and their function in the maintenance of nuclear and mitochondrial genome integrity. Mutat Res. 2012; 733:21–33.
Article
4. Crider KS, Yang TP, Berry RJ, Bailey LB. Folate and DNA methylation: a review of molecular mechanisms and the evidence for folate\'s role. Adv Nutr. 2012; 3:21–38.
Article
5. Paul L, Cattaneo M, D'Angelo A, Sampietro F, Fermo I, Razzari C, Fontana G, Eugene N, Jacques PF, Selhub J. Telomere length in peripheral blood mononuclear cells is associated with folate status in men. J Nutr. 2009; 139:1273–1278.
Article
6. Richards JB, Valdes AM, Gardner JP, Kato BS, Siva A, Kimura M, Lu X, Brown MJ, Aviv A, Spector TD. Homocysteine levels and leukocyte telomere length. Atherosclerosis. 2008; 200:271–277.
Article
7. Bull CF, OCallaghan NJ, Mayrhofer G, Fenech MF. Telomere length in lymphocytes of older South Australian men may be inversely associated with plasma homocysteine. Rejuvenation Res. 2009; 12:341–349.
Article
8. Liu JJ, Prescott J, Giovannucci E, Hankinson SE, Rosner B, De Vivo I. One-carbon metabolism factors and leukocyte telomere length. Am J Clin Nutr. 2013; 97:794–799.
Article
9. Paul L, Jacques PF, Aviv A, Vasan RS, DAgostino RB, Levy D, Selhub J. High plasma folate is negatively associated with leukocyte telomere length in Framingham Offspring cohort. Eur J Nutr. 2015; 54:235–241.
Article
10. Rane G, Koh WP, Kanchi MM, Wang R, Yuan JM, Wang X. Association between leukocyte telomere length and plasma homocysteine in a Singapore Chinese population. Rejuvenation Res. 2015; 18:203–210.
Article
11. Zhang D, Wen X, Wu W, Xu E, Zhang Y, Cui W. Homocysteine-related hTERT DNA demethylation contributes to shortened leukocyte telomere length in atherosclerosis. Atherosclerosis. 2013; 231:173–179.
Article
12. Zhang DH, Wen XM, Zhang L, Cui W. DNA methylation of human telomerase reverse transcriptase associated with leukocyte telomere length shortening in hyperhomocysteinemia-type hypertension in humans and in a rat model. Circ J. 2014; 78:1915–1923.
Article
13. Mather KA, Jorm AF, Parslow RA, Christensen H. Is telomere length a biomarker of aging? A review. J Gerontol A Biol Sci Med Sci. 2011; 66:202–213.
Article
14. Saretzki G, Von Zglinicki T. Replicative aging, telomeres, and oxidative stress. Ann N Y Acad Sci. 2002; 959:24–29.
Article
15. Bull CF, Mayrhofer G, O'Callaghan NJ, Au AY, Pickett HA, Low GK, Zeegers D, Hande MP, Fenech MF. Folate deficiency induces dysfunctional long and short telomeres; both states are associated with hypomethylation and DNA damage in human WIL2-NS cells. Cancer Prev Res (Phila). 2014; 7:128–138.
Article
16. Tyagi N, Sedoris KC, Steed M, Ovechkin AV, Moshal KS, Tyagi SC. Mechanisms of homocysteine-induced oxidative stress. Am J Physiol Heart Circ Physiol. 2005; 289:H2649–H2656.
Article
17. Baik I, Kim J, Abbott RD, Joo S, Jung K, Lee S, Shim J, In K, Kang K, Yoo S, Shin C. Association of snoring with chronic bronchitis. Arch Intern Med. 2008; 168:167–173.
Article
18. Cawthon RM. Telomere measurement by quantitative PCR. Nucleic Acids Res. 2002; 30:e47.
Article
19. Kushner I, Samols D, Magrey M. A unifying biologic explanation for "high-sensitivity" C-reactive protein and "low-grade" inflammation. Arthritis Care Res (Hoboken). 2010; 62:442–446.
Article
20. Moores CJ, Fenech M, O'Callaghan NJ. Telomere dynamics: the influence of folate and DNA methylation. Ann N Y Acad Sci. 2011; 1229:76–88.
Article
21. Wong JY, De Vivo I, Lin X, Fang SC, Christiani DC. The relationship between inflammatory biomarkers and telomere length in an occupational prospective cohort study. PLoS One. 2014; 9:e87348.
Article
22. Blount BC, Mack MM, Wehr CM, MacGregor JT, Hiatt RA, Wang G, Wickramasinghe SN, Everson RB, Ames BN. Folate deficiency causes uracil misincorporation into human DNA and chromosome breakage: implications for cancer and neuronal damage. Proc Natl Acad Sci U S A. 1997; 94:3290–3295.
Article
23. Ventura E, Durant R, Jaussent A, Picot MC, Morena M, Badiou S, Dupuy AM, Jeandel C, Cristol JP. Homocysteine and inflammation as main determinants of oxidative stress in the elderly. Free Radic Biol Med. 2009; 46:737–744.
Article
24. Mendes RH, Mostarda C, Candido GO, Moraes-Silva IC, D'Almeida V, Belló-Klein A, Irigoyen MC, Rigatto K. Moderate hyperhomocysteinemia provokes dysfunction of cardiovascular autonomic system and liver oxidative stress in rats. Auton Neurosci. 2014; 180:43–47.
Article
25. Wilcken DE, Wang XL, Adachi T, Hara H, Duarte N, Green K, Wilcken B. Relationship between homocysteine and superoxide dismutase in homocystinuria: possible relevance to cardiovascular risk. Arterioscler Thromb Vasc Biol. 2000; 20:1199–1202.
Article
26. Schroecksnadel K, Frick B, Wirleitner B, Winkler C, Schennach H, Fuchs D. Moderate hyperhomocysteinemia and immune activation. Curr Pharm Biotechnol. 2004; 5:107–118.
Article
27. Durand P, Prost M, Loreau N, Lussier-Cacan S, Blache D. Impaired homocysteine metabolism and atherothrombotic disease. Lab Invest. 2001; 81:645–672.
Article
28. Chambers JC, Obeid OA, Kooner JS. Physiological increments in plasma homocysteine induce vascular endothelial dysfunction in normal human subjects. Arterioscler Thromb Vasc Biol. 1999; 19:2922–2927.
Article
29. Yakub M, Iqbal MP, Iqbal R. Dietary patterns are associated with hyperhomocysteinemia in an urban Pakistani population. J Nutr. 2010; 140:1261–1266.
Article
30. Daniali L, Benetos A, Susser E, Kark JD, Labat C, Kimura M, Desai K, Granick M, Aviv A. Telomeres shorten at equivalent rates in somatic tissues of adults. Nat Commun. 2013; 4:1597.
Article
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