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
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.
Muezzinler A, Zaineddin AK, Brenner H. A systematic review of leukocyte telomere length and age in adults. Ageing Res Rev. 2013; 12: 509–519.
Cawthon RM. Telomere measurement by quantitative pcr. Nucleic Acids Res. 2002; 30: e47.
Cawthon RM. Telomere length measurement by a novel monochrome multiplex quantitative pcr method. Nucleic Acids Res. 2009; 37: e21.
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.
Blackburn EH. Structure and function of telomeres. Nature. 1991; 350: 569–573.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Meramat A, Rajab NF, Shahar S, Sharif R. Cognitive impairment, genomic instability and trace elements. J Nutr Health Aging. 2015; 19: 48–57.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Bekaert S, De Meyer T, Van Oostveldt P. Telomere attrition as ageing biomarker. Anticancer Res. 2005; 25: 3011–3021.
Fyhrquist F, Saijonmaa O. Telomere length and cardiovascular aging. Ann Med. 2012; 44 Suppl 1: S138–142.
Fyhrquist F, Saijonmaa O, Strandberg T. The roles of senescence and telomere shortening in cardiovascular disease. Nat Rev Cardiol. 2013; 10: 274–283.
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.
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.
Proctor CJ, Kirkwood TB. Modelling telomere shortening and the role of oxidative stress. Mech Ageing Dev. 2002; 123: 351–363.
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.
van Steensel B, Smogorzewska A, de Lange T. Trf2 protects human telomeres from end-to-end fusions. Cell. 1998; 92: 401–413.
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.
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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