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Associations of buccal cell telomere length with daily intake of β-carotene or α-tocopherol are dependent on carotenoid metabolism-related gene polymorphisms in healthy Japanese adults

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The journal of nutrition, health & aging

Abstract

Objective

Telomere length shortening is modulated not only by aging, but also by both genetic and environmental factors. The aim of this study was to investigate the interactions between antioxidant nutrient metabolism-related gene single nucleotide polymorphisms (the genetic factors) and nutrient intake (the environmental factors) in their effects on telomere length shortening.

Setting & participants

Data were collected on the relative telomere lengths (RTLs) of buccal cells and the habitual food intake of 70 healthy Japanese adults.

Measurements

All subjects were genotyped for two common single nucleotide polymorphisms: rs6564851 in the β-carotene-15,15’-mono-oxygenase 1 (BCMO1) gene and rs362090 in the intestine-specific homeobox (ISX) gene.

Results

Univariate analysis revealed that buccal RTL was not significantly modulated by either age or gender. Then, we subdivided the study population into four groups based on combinations of the rs6564851 and rs362090 genotypes. After this subdivision, we showed a positive effect of daily α- or β-carotene intake on buccal RTL in the ISX rs362090 G-allele carrier + BCMO1 rs6564851 GG-genotype group (p = 0.026). Additionally, daily intake of another antioxidative fat-soluble vitamin, α-tocopherol, was positively associated with buccal RTL in the ISX rs362090 AA-homozygote + BCMO1 rs6564851 T-allele carrier group (p = 0.037).

Conclusion

Our study clearly indicates that high dietary intake of the antioxidants α, β-carotene and α-tocopherol protects buccal cells from RTL shortening, depending on the genetic background of antioxidant vitamin-related genes.

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Abbreviations

Ct:

cycle threshold

FFQ:

food frequency questionnaire

MMqPCR:

monochrome multiplex quantitative polymerase chain reaction

RTL:

relative telomere length

scg:

single-copy gene

SNP:

single nucleotide polymorphism

References

  1. Fehrer C, Voglauer R, Wieser M, Pfister G, Brunauer R, Cioca D, Grubeck-Loebenstein B, Lepperdinger G. Techniques in gerontology: Cell lines as standards for telomere length and telomerase activity assessment. Exp Gerontol. 2006; 41: 648–651.

    Article  CAS  PubMed  Google Scholar 

  2. Muezzinler A, Zaineddin AK, Brenner H. A systematic review of leukocyte telomere length and age in adults. Ageing Res Rev. 2013; 12: 509–519.

    Article  PubMed  Google Scholar 

  3. Cawthon RM. Telomere measurement by quantitative pcr. Nucleic Acids Res. 2002; 30: e47.

    Article  PubMed Central  PubMed  Google Scholar 

  4. Cawthon RM. Telomere length measurement by a novel monochrome multiplex quantitative pcr method. Nucleic Acids Res. 2009; 37: e21.

    Article  PubMed Central  PubMed  Google Scholar 

  5. Lan Q, Cawthon R, Shen M, Weinstein SJ, Virtamo J, Lim U, Hosgood HD, 3rd, Albanes D, Rothman N. A prospective study of telomere length measured by monochrome multiplex quantitative pcr and risk of non-hodgkin lymphoma. Clin Cancer Res. 2009; 15: 7429–7433.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Blackburn EH. Structure and function of telomeres. Nature. 1991; 350: 569–573.

    Article  CAS  PubMed  Google Scholar 

  7. Theall KP, McKasson S, Mabile E, Dunaway LF, Drury SS. Early hits and long-term consequences: Tracking the lasting impact of prenatal smoke exposure on telomere length in children. Am J Public Health. 2013; 103 Suppl 1: S133–135.

    Article  PubMed Central  PubMed  Google Scholar 

  8. Kroenke CH, Epel E, Adler N, Bush NR, Obradovic J, Lin J, Blackburn E, Stamperdahl JL, Boyce WT. Autonomic and adrenocortical reactivity and buccal cell telomere length in kindergarten children. Psychosom Med. 2011; 73: 533–540.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Broberg K, Bjork J, Paulsson K, Hoglund M, Albin M. Constitutional short telomeres are strong genetic susceptibility markers for bladder cancer. Carcinogenesis. 2005; 26: 1263–1271.

    Article  CAS  PubMed  Google Scholar 

  10. Capezzone M, Cantara S, Marchisotta S, Busonero G, Formichi C, Benigni M, Capuano S, Toti P, Pazaitou-Panayiotou K, Caruso G, Carli AF, Palummo N, Pacini F. Telomere length in neoplastic and nonneoplastic tissues of patients with familial and sporadic papillary thyroid cancer. J Clin Endocrinol Metab. 2011; 96: E1852–1856.

    Article  CAS  PubMed  Google Scholar 

  11. Drury SS, Shirtcliff EA, Shachet A, Phan J, Mabile E, Brett ZH, Wren M, Esteves K, Theall KP. Growing up or growing old? Cellular aging linked with testosterone reactivity to stress in youth. Am J Med Sci. 2014; 348: 92–100.

    Article  PubMed Central  PubMed  Google Scholar 

  12. Drury SS, Mabile E, Brett ZH, Esteves K, Jones E, Shirtcliff EA, Theall KP. The association of telomere length with family violence and disruption. Pediatrics. 2014; 134: e128–137.

    Article  PubMed Central  PubMed  Google Scholar 

  13. Houben JM, Moonen HJ, van Schooten FJ, Hageman GJ. Telomere length assessment: Biomarker of chronic oxidative stress? Free Radic Biol Med. 2008; 44: 235–246.

    Article  CAS  PubMed  Google Scholar 

  14. O’Callaghan NJ, Bull C, Fenech M. Elevated plasma magnesium and calcium may be associated with shorter telomeres in older south australian women. J Nutr Health Aging. 2014; 18: 131–136.

    Article  PubMed  Google Scholar 

  15. Kiecolt-Glaser JK, Epel ES, Belury MA, Andridge R, Lin J, Glaser R, Malarkey WB, Hwang BS, Blackburn E. Omega-3 fatty acids, oxidative stress, and leukocyte telomere length: A randomized controlled trial. Brain Behav Immun. 2013; 28: 16–24.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Ornish D, Lin J, Daubenmier J, Weidner G, Epel E, Kemp C, Magbanua MJ, Marlin R, Yglecias L, Carroll PR, Blackburn EH. Increased telomerase activity and comprehensive lifestyle changes: A pilot study. Lancet Oncol. 2008; 9: 1048–1057.

    Article  CAS  PubMed  Google Scholar 

  17. Farzaneh-Far R, Lin J, Epel ES, Harris WS, Blackburn EH, Whooley MA. Association of marine omega-3 fatty acid levels with telomeric aging in patients with coronary heart disease. JAMA. 2010; 303: 250–257.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. O’Callaghan N, Parletta N, Milte CM, Benassi-Evans B, Fenech M, Howe PR. Telomere shortening in elderly individuals with mild cognitive impairment may be attenuated with omega-3 fatty acid supplementation: A randomized controlled pilot study. Nutrition. 2014; 30: 489–491.

    Article  PubMed  Google Scholar 

  19. Garcia-Calzon S, Moleres A, Martinez-Gonzalez MA, Martinez JA, Zalba G, Marti A. Dietary total antioxidant capacity is associated with leukocyte telomere length in a children and adolescent population. Clin Nutr. 2014.

    Google Scholar 

  20. Meramat A, Rajab NF, Shahar S, Sharif R. Cognitive impairment, genomic instability and trace elements. J Nutr Health Aging. 2015; 19: 48–57.

    Article  CAS  PubMed  Google Scholar 

  21. Ferrucci L, Perry JR, Matteini A, Perola M, Tanaka T, Silander K, Rice N, Melzer D, Murray A, Cluett C, Fried LP, Albanes D, Corsi AM, Cherubini A, Guralnik J, Bandinelli S, Singleton A, Virtamo J, Walston J, Semba RD, Frayling TM. Common variation in the beta-carotene 15,15’-monooxygenase 1 gene affects circulating levels of carotenoids: A genome-wide association study. Am J Hum Genet. 2009; 84: 123–133.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Perry JR, Ferrucci L, Bandinelli S, Guralnik J, Semba RD, Rice N, Melzer D, Saxena R, Scott LJ, McCarthy MI, Hattersley AT, Zeggini E, Weedon MN, Frayling TM. Circulating beta-carotene levels and type 2 diabetes-cause or effect? Diabetologia. 2009; 52: 2117–2121.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Leung WC, Hessel S, Meplan C, Flint J, Oberhauser V, Tourniaire F, Hesketh JE, von Lintig J, Lietz G. Two common single nucleotide polymorphisms in the gene encoding beta-carotene 15,15’-monoxygenase alter beta-carotene metabolism in female volunteers. FASEB J. 2009; 23: 1041–1053.

    Article  CAS  PubMed  Google Scholar 

  24. Lobo GP, Amengual J, Li HN, Golczak M, Bonet ML, Palczewski K, von Lintig J. Beta,beta-carotene decreases peroxisome proliferator receptor gamma activity and reduces lipid storage capacity of adipocytes in a beta,beta-carotene oxygenase 1-dependent manner. J Biol Chem. 2010; 285: 27891–27899.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Lobo GP, Hessel S, Eichinger A, Noy N, Moise AR, Wyss A, Palczewski K, von Lintig J. Isx is a retinoic acid-sensitive gatekeeper that controls intestinal beta,beta-carotene absorption and vitamin a production. FASEB J. 2010; 24: 1656–1666.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Thomas P, NJ OC, Fenech M. Telomere length in white blood cells, buccal cells and brain tissue and its variation with ageing and alzheimer’s disease. Mech Ageing Dev. 2008; 129: 183–190.

    Article  CAS  PubMed  Google Scholar 

  27. Thomas P, Wang YJ, Zhong JH, Kosaraju S, O’Callaghan NJ, Zhou XF, Fenech M. Grape seed polyphenols and curcumin reduce genomic instability events in a transgenic mouse model for alzheimer’s disease. Mutat Res. 2009; 661: 25–34.

    Article  CAS  PubMed  Google Scholar 

  28. Gadalla SM, Cawthon R, Giri N, Alter BP, Savage SA. Telomere length in blood, buccal cells, and fibroblasts from patients with inherited bone marrow failure syndromes. Aging (Albany NY). 2010; 2: 867–874.

    Google Scholar 

  29. Wong LS, Huzen J, de Boer RA, van Gilst WH, van Veldhuisen DJ, van der Harst P. Telomere length of circulating leukocyte subpopulations and buccal cells in patients with ischemic heart failure and their offspring. PLoS One. 2011; 6: e23118.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Hou L, Andreotti G, Baccarelli AA, Savage S, Hoppin JA, Sandler DP, Barker J, Zhu ZZ, Hoxha M, Dioni L, Zhang X, Koutros S, Freeman LE, Alavanja MC. Lifetime pesticide use and telomere shortening among male pesticide applicators in the agricultural health study. Environ Health Perspect. 2013; 121: 919–924.

    Article  PubMed Central  PubMed  Google Scholar 

  31. Walcott F, Rajaraman P, Gadalla SM, Inskip PD, Purdue MP, Albanes D, Orr E, De Vivo I, Savage SA. Telomere length and risk of glioma. Cancer Epidemiol. 2013; 37: 935–938.

    Article  PubMed Central  PubMed  Google Scholar 

  32. Shan M, Yang X, Ezzati M, Chaturvedi N, Coady E, Hughes A, Shi Y, Yang M, Zhang Y, Baumgartner J. A feasibility study of the association of exposure to biomass smoke with vascular function, inflammation, and cellular aging. Environ Res. 2014; 135C: 165–172.

    Article  Google Scholar 

  33. Entringer S, Epel ES, Lin J, Blackburn EH, Buss C, Simhan HN, Wadhwa PD. Maternal estriol (e) concentrations in early gestation predict infant telomere length. J Clin Endocrinol Metab. 2014: jc20142744.

    Google Scholar 

  34. Hewakapuge S, van Oorschot RA, Lewandowski P, Baindur-Hudson S. Investigation of telomere lengths measurement by quantitative real-time pcr to predict age. Leg Med (Tokyo). 2008; 10: 236–242.

    Article  CAS  Google Scholar 

  35. Bekaert S, De Meyer T, Van Oostveldt P. Telomere attrition as ageing biomarker. Anticancer Res. 2005; 25: 3011–3021.

    CAS  PubMed  Google Scholar 

  36. Fyhrquist F, Saijonmaa O. Telomere length and cardiovascular aging. Ann Med. 2012; 44 Suppl 1: S138–142.

    Article  CAS  PubMed  Google Scholar 

  37. Fyhrquist F, Saijonmaa O, Strandberg T. The roles of senescence and telomere shortening in cardiovascular disease. Nat Rev Cardiol. 2013; 10: 274–283.

    Article  CAS  PubMed  Google Scholar 

  38. Marcon F, Siniscalchi E, Crebelli R, Saieva C, Sera F, Fortini P, Simonelli V, Palli D. Diet-related telomere shortening and chromosome stability. Mutagenesis. 2012; 27: 49–57.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Makpol S, Zainuddin A, Rahim NA, Yusof YA, Ngah WZ. Alpha-tocopherol modulates hydrogen peroxide-induced DNA damage and telomere shortening of human skin fibroblasts derived from differently aged individuals. Planta Med. 2010; 76: 869–875.

    Article  CAS  PubMed  Google Scholar 

  40. Proctor CJ, Kirkwood TB. Modelling telomere shortening and the role of oxidative stress. Mech Ageing Dev. 2002; 123: 351–363.

    Article  CAS  PubMed  Google Scholar 

  41. Serra V, von Zglinicki T, Lorenz M, Saretzki G. Extracellular superoxide dismutase is a major antioxidant in human fibroblasts and slows telomere shortening. J Biol Chem. 2003; 278: 6824–6830.

    Article  CAS  PubMed  Google Scholar 

  42. van Steensel B, Smogorzewska A, de Lange T. Trf2 protects human telomeres from end-to-end fusions. Cell. 1998; 92: 401–413.

    Article  PubMed  Google Scholar 

  43. Makpol S, Abidin AZ, Sairin K, Mazlan M, Top GM, Ngah WZ. Gamma-tocotrienol prevents oxidative stress-induced telomere shortening in human fibroblasts derived from different aged individuals. Oxid Med Cell Longev. 2010; 3: 35–43.

    Article  PubMed Central  PubMed  Google Scholar 

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Correspondence to Yoshihiro Shidoji.

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Yabuta, S., Masaki, M. & Shidoji, Y. Associations of buccal cell telomere length with daily intake of β-carotene or α-tocopherol are dependent on carotenoid metabolism-related gene polymorphisms in healthy Japanese adults. J Nutr Health Aging 20, 267–274 (2016). https://doi.org/10.1007/s12603-015-0577-x

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  • DOI: https://doi.org/10.1007/s12603-015-0577-x

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