Abstract
Background
Excess iron levels can induce oxidative stress and could therefore affect telomere
attrition. However, little is known about the impact of body iron status on telomere
length.
Objective
Our aim was to examine the association between serum ferritin concentrations, an indicator
of body iron status, and leukocyte telomere length in US adults.
Design
We conducted a nationwide, population-based, cross-sectional study.
Participants/setting
We used data from the National Health and Nutrition Examination Survey (NHANES) 1999-2002.
We included 7,336 adults aged 20 years or older who had available data on serum ferritin
levels and telomere length. High ferritin levels were defined as a serum ferritin
level >200 ng/mL (449.4 pmol/L) in women and >300 ng/mL (674.1 pmol/L) in men. Low
ferritin levels were defined as a serum ferritin level <30 ng/mL (67.4 pmol/L).
Main outcome measures
Leukocyte telomere length was assayed using the quantitative polymerase chain reaction
method.
Statistical analyses
Linear regression with survey weights was performed to estimate the association between
serum ferritin levels and telomere length.
Results
The prevalence of adults with high and low serum ferritin levels was 10.9% and 17.6%,
respectively. High ferritin levels were inversely associated with telomere length
compared to normal ferritin levels. After adjustment for demographic, socioeconomic
and lifestyle factors, body mass index, C-reactive protein, and leukocyte cell type
composition, the β coefficient for log-transformed telomere length was –0.020 (standard
error [SE]=0.009; P=0.047). The association was stronger in adults aged 65 years or older (β coefficient
–0.081, SE=0.017; P<0.001) than in adults 20 to 44 years old (β coefficient –0.023, SE=0.019; P=0.24) or adults aged 45 to 64 years old (β coefficient 0.024, SE=0.015; P=0.10) (P for interaction 0.003). Low ferritin levels were not significantly associated with
telomere length compared with normal ferritin levels.
Conclusions
In a US nationally representative population, high body iron status was associated
with shorter telomeres, especially in adults aged 65 years or older.
Keywords
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References
- Structure and function of telomeres.Nature. 1991; 350: 569-573
- The hallmarks of aging.Cell. 2013; 153: 1194-1217
- Telomere length variations in aging and age-related diseases.Curr Aging Sci. 2014; 7: 161-167
- Telomere length in epidemiology: A biomarker of aging, age-related disease, both, or neither?.Epidemiol Rev. 2013; 35: 112-131
- Telomeres and human disease: Ageing, cancer and beyond.Nat Rev Genet. 2005; 6: 611-622
- Telomere length assessment: Biomarker of chronic oxidative stress?.Free Radic Biol Med. 2008; 44: 235-246
- Telomere length in early life predicts lifespan.Proc Natl Acad Sci U S A. 2012; 109: 1743-1748
- Leucocyte telomere length and risk of type 2 diabetes mellitus: New prospective cohort study and literature-based meta-analysis.PLoS One. 2014; 9: e112483
- Leucocyte telomere length and risk of cardiovascular disease: Systematic review and meta-analysis.BMJ. 2014; 349: g4227
- Telomere length shortening and Alzheimer disease—A Mendelian randomization study.JAMA Neurol. 2015; 72: 1202-1203
- Meta-analysis of telomere length in Alzheimer's disease.J Gerontol A Biol Sci Med Sci. 2016; 71: 1069-1073
- Leukocyte telomere length and mortality in the National Health and Nutrition Examination Survey, 1999-2002.Epidemiology. 2015; 26: 528-535
- Maternal and genetic factors determine early life telomere length.Proc Biol Sci. 2015; 282: 20142263
- The heritability of leucocyte telomere length dynamics.J Med Genet. 2015; 52: 297-302
- Heritability of telomere length in a study of long-lived families.Neurobiol Aging. 2015; 36: 2785-2790
- Genetic determination of telomere size in humans: A twin study of three age groups.Am J Hum Genet. 1994; 55: 876-882
- Nature vs nurture interplay between the genetic control of telomere length and environmental factors.Cell Cycle. 2013; 12: 3465-3470
- Environmental stresses disrupt telomere length homeostasis.PLoS Genet. 2013; 9: e1003721
- Shared environmental factors associated with telomere length maintenance in elderly male twins.Aging Cell. 2007; 6: 709-713
- Pathways linking the early environment to long-term health and lifespan.Prog Biophys Mol Biol. 2011; 106: 323-336
- The roles of iron in health and disease.Mol Aspects Med. 2001; 22: 1-87
- The epidemiology of global micronutrient deficiencies.Ann Nutr Metab. 2015; 66: 22-33
- Dietary iron intake, body iron stores, and the risk of type 2 diabetes: A systematic review and meta-analysis.BMC Med. 2012; 10: 119
- Total and cause-specific mortality by moderately and markedly increased ferritin concentrations: General population study and metaanalysis.Clin Chem. 2014; 60: 1419-1428
- The association of ferritin with cardiovascular and all-cause mortality in community-dwellers: The English longitudinal study of ageing.PLoS One. 2017; 12: e0178994
- Telomere length and elevated iron: The influence of phenotype and HFE genotype.Am J Hematol. 2013; 88: 492-496
- Impact of oxidative stress in premature aging and iron overload in hemodialysis patients.Oxid Med Cell Longev. 2016; 2016: 1578235
- Rethinking ferritin cutoffs for iron deficiency and overload.Lancet Haematol. 2014; 1: e92-e94
- Hemochromatosis and iron-overload screening in a racially diverse population.N Engl J Med. 2005; 352: 1769-1778
- Interpreting raised serum ferritin levels.BMJ. 2015; 351: h3692
- Assessing the Iron Status of Populations.2nd ed. World Health Organization, Geneva, Switzerland2004
- Telomere measurement by quantitative PCR.Nucleic Acids Res. 2002; 30: e47
- Socioeconomic status, health behavior, and leukocyte telomere length in the National Health and Nutrition Examination Survey, 1999-2002.Soc Sci Med. 2013; 85: 1-8
- National health and nutrition examination survey: Analytic guidelines, 1999-2010.Vital Health Stat 2. 2013 Sep; : 1-24
Centers for Disease Control and Prevention, National Center for Health Statistics. Adult Tobacco Use Information Glossary. https://www.cdc.gov/nchs/nhis/tobacco/tobacco_glossary.htm. Updated August 29, 2017; Accessed October 5, 2018.
US Department of Agriculture, Agricultural Research Service, Beltsville Human Nutrition Research Center, Food Surveys Research Group. USDA Automated Multiple-Pass Method for Dietary Recalls. Beltsville, MD: US Department of Agriculture; 2016.
- 2008 Physical Activity Guidelines for Americans.US Department of Health and Human Services, Washington, DC2008
- Leukocyte telomere length in relation to 17 biomarkers of cardiovascular disease risk: A cross-sectional study of US adults.PLoS Med. 2016; 13: e1002188
- NHANES Survey Methods and Analytic Guidelines.(Accessed October 5, 2018)
SAS [computer program]. Version 9.4. Cary, NC: SAS Institute; 2013.
- Elevated transferrin saturation, health-related quality of life and telomere length.Biometals. 2014; 27: 135-141
- Transferrin saturation concentrations associated with telomeric ageing: A population-based study.Br J Nutr. 2017; 117: 1693-1701
- The influence of oxidative stress induced by iron on telomere length.Environ Toxicol Pharmacol. 2015; 40: 931-935
- Chronic oxidative stress induces a tissue-specific reduction in telomere length in CAST/Ei mice.Free Radic Biol Med. 2008; 44: 1592-1598
- Asp-Ala-His-Lys (DAHK) inhibits copper-induced oxidative DNA double strand breaks and telomere shortening.Biochem Biophys Res Commun. 2001; 282: 356-360
- Site-specific DNA damage at the GGG sequence by UVA involves acceleration of telomere shortening.Biochemistry. 2001; 40: 4763-4768
- Coenzyme Q10 changes are associated with metabolic syndrome.Clin Chim Acta. 2004; 344: 173-179
- Exercise at old age: Does it increase or alleviate oxidative stress?.Ann N Y Acad Sci. 2001; 928: 236-247
- Dietary supplements and mortality rate in older women: The Iowa Women's Health Study.Arch Intern Med. 2011; 171: 1625-1633
- Ferritin levels, inflammatory biomarkers, and mortality in peripheral arterial disease: A substudy of the Iron (Fe) and Atherosclerosis Study (FeAST) Trial.J Vasc Surg. 2010; 51: 1498-1503
- Management of elevated serum ferritin levels.Gastroenterol Hepatol (N Y). 2008; 4: 333-334
Biography
B. Liu is a postdoctoral research scholar, Department of Epidemiology, College of Public Health, University of Iowa, Iowa City.
Biography
Y. Sun is a postdoctoral research scholar, Department of Epidemiology, College of Public Health, University of Iowa, Iowa City.
Biography
G. Xu is a PhD candidate, Department of Epidemiology, College of Public Health, University of Iowa, Iowa City.
Biography
L. G. Snetselaar is a professor, Department of Epidemiology, College of Public Health, University of Iowa, Iowa City.
Biography
R. B. Wallace is a professor, Department of Epidemiology,
Biography
G. Ludewig is a professor, Department of Occupational and Environmental Health, all with the College of Public Health, University of Iowa, Iowa City.
Biography
W. Bao is an assistant professor, Department of Epidemiology, College of Public Health; a member of the Obesity Research and Education Initiative; and a member of the Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City.
Article info
Publication history
Published online: December 15, 2018
Accepted:
September 11,
2018
Received:
April 3,
2018
Footnotes
STATEMENT OF POTENTIAL CONFLICT OF INTEREST No potential conflict of interest was reported by the authors.
FUNDING/SUPPORT This research was supported by the National Institutes of Health through the University of Iowa Environmental Health Sciences Research Center, National Institute of Environmental Health Sciences/National Institutes of Health P30 ES005605. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
AUTHOR CONTRIBUTIONS W. Bao has full access to all of the data in this study and assumes responsibility for study supervision. W. Bao and B. Liu contributed to the conception and design of the study. B. Liu performed the statistical analyses and drafted the manuscript. All authors contributed to the acquisition, analysis, or interpretation of the data, and critically revised the manuscript for important intellectual content.
Identification
Copyright
© 2019 by the Academy of Nutrition and Dietetics.
