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The impact of pathogen burden on leukocyte telomere length in the Multi-Ethnic Study of Atherosclerosis

  • A. E. AIELLO (a1), B. JAYABALASINGHAM (a2), A. M. SIMANEK (a3), A. DIEZ-ROUX (a4), L. FEINSTEIN (a1) (a5), H. C. S. MEIER (a3), B. L. NEEDHAM (a6) and J. B. DOWD (a2)...

Several infections have been linked to telomere shortening and in some cases these associations have varied by sex. We assessed the association between seropositivity to four persistent pathogens (cytomegalovirus (CMV), herpes simplex virus-1, Helicobacter pylori, Chlamydia pneumoniae), and total pathogen burden on leukocyte telomere length in a diverse US sample. Data came from the Multi-Ethnic Study of Atherosclerosis, a population-based cohort study. We utilized cross-sectional survey data, and biological samples from participants tested for pathogens and telomere length (N = 163). Linear regression was used to examine the association between seropositivity for individual pathogens as well as total pathogen burden and telomere length, adjusting for various confounders. CMV seropositivity and increased total pathogen burden level were significantly associated with shorter telomere length among females (β = −0·1204 (standard error (s.e.) 0·06), P = 0·044) and (β = −0·1057 (s.e. = 0·05), P = 0·033), respectively. There was no statistically significant association among males. Our findings suggest that prevention or treatment of persistent pathogens, in particular CMV, may play an important role in reducing telomere shortening over the life course among women. Future research is needed to confirm these novel findings in larger longitudinal samples.

Corresponding author
*Author for correspondence: A. E. Aiello, 135 Dauer Dr, 2101C McGavran-Greenberg Hall, Chapel Hill, NC 27599, USA. (Email:
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1. Olovnikov, AM. A theory of marginotomy. The incomplete copying of template margin in enzymic synthesis of polynucleotides and biological significance of the phenomenon. Journal of Theoretical Biology 1973; 41(1): 181190.
2. Kroenke, CH, et al. Telomerase, telomere length, and coronary artery calcium in black and white men in the CARDIA study. Atherosclerosis 2012; 220(2): 506512.
3. Sanders, JL, et al. Leukocyte telomere length is associated with noninvasively measured age-related disease: The Cardiovascular Health Study. The Journals of Gerontology Series A, Biological Sciences and Medical Sciences 2012; 67(4): 409416.
4. Hou, L, et al. Telomere length in peripheral leukocyte DNA and gastric cancer risk. Cancer Epidemiology, Biomarkers & Prevention: A Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology 2009; 18(11): 31033109.
5. Wentzensen, IM, et al. The association of telomere length and cancer: a meta-analysis. Cancer Epidemiology, Biomarkers & Prevention: A Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology 2011; 20(6): 12381250.
6. Deelen, J, et al. Leukocyte telomere length associates with prospective mortality independent of immune-related parameters and known genetic markers. International Journal of Epidemiology 2014; 43(3): 878886.
7. O'Donovan, A, et al. Cumulative inflammatory load is associated with short leukocyte telomere length in the Health, Aging and Body Composition Study. Public Library of Science One 2011; 6(5): e19687.
8. Wong, JY, et al. The relationship between inflammatory biomarkers and telomere length in an occupational prospective cohort study. Public Library of Science One 2014; 9(1): e87348.
9. Dowd, JB, et al. Cytomegalovirus is associated with reduced telomerase activity in the Whitehall II cohort. Experimental Gerontology 2013; 48(4): 385390.
10. Effros, RB. Telomere/telomerase dynamics within the human immune system: effect of chronic infection and stress. Experimental Gerontology 2011; 46(2–3): 135140.
11. Gladych, MM, Wojtyla, AA, Rubis, BB. Human telomerase expression regulation. Biochemistry and Cell Biology 2011; 89(4): 359376.
12. Barrett, ELB, Richardson, DS. Sex differences in telomeres and lifespan. Aging Cell 2011; 10(6): 913921.
13. Giefing-Kroll, C, et al. How sex and age affect immune responses, susceptibility to infections, and response to vaccination. Aging Cell 2015; 14(3): 309321.
14. Klein, SL, Marriott, I, Fish, EN. Sex-based differences in immune function and responses to vaccination. Transactions of the Royal Society of Tropical Medicine and Hygiene 2015; 109(1): 915.
15. Bild, DE. Multi-Ethnic Study of Atherosclerosis: objectives and design. American journal of epidemiology 2002; 156(9): 871881.
16. Aiello, AE, et al. Socioeconomic and psychosocial gradients in cardiovascular pathogen burden and immune response: the Multi-Ethnic Study of Atherosclerosis. Brain, Behavior, and Immunity 2009; 23(5): 663671.
17. Diez Roux, AV, et al. Race/ethnicity and telomere length in the Multi-Ethnic Study of Atherosclerosis. Aging Cell 2009; 8(3): 251257.
18. Zhu, J, et al. Effects of total pathogen burden on coronary artery disease risk and C-reactive protein levels. American Journal of Cardiology 2000; 85(2): 140146.
19. Lutsey, PL, et al. Serological evidence of infections and type 2 diabetes: the Multi-Ethnic Study of Atherosclerosis. Diabetic Medicine 2009; 26(2): 149152.
20. Cawthon, RM. Telomere measurement by quantitative PCR. Nucleic acids research 2002; 30(10): e47.
21. American Diabetes Association. Diagnosis and Classification of Diabetes Mellitus. 2004, pp. S5S10. Available at:
22. Golden, SH, et al. Depression and type 2 diabetes mellitus: the Multi-Ethnic Study of Atherosclerosis. Psychosomatic Medicine 2007; 69(6): 529536.
23. Hearps, AC, et al. HIV infection and aging of the innate immune system. Sexual Health 2011; 8(4): 453464.
24. Kitay-Cohen, Y, et al. Telomere length in Hepatitis C. Cancer Genetics and Cytogenetics 2008; 187(1): 3438.
25. Zhang, Y, et al. Telomere length in peripheral blood lymphocytes contributes to the development of HPV-associated oropharyngeal carcinoma. Cancer Research 2013; 73(19): 59966003.
26. van de Berg, PJ, et al. Cytomegalovirus infection reduces telomere length of the circulating T cell pool. Journal of Immunology 2010; 184(7): 34173423.
27. Aslan, R, et al. Helicobacter pylori eradication increases telomere length in gastric mucosa. Hepato-Gastroenterology 2013; 60(123): 601604.
28. Klein, SL. Sex influences immune responses to viruses, and efficacy of prophylaxis and treatments for viral diseases. BioEssays 2012; 34(12): 10501059.
29. Muenchhoff, M, Goulder, PJR. Sex differences in pediatric infectious diseases. The Journal of Infectious Diseases 2014; 209(Suppl. 3): S120S126.
30. Hewagama, A, et al. Stronger inflammatory/cytotoxic T-cell response in women identified by microarray analysis. Genes and Immunity 2009; 10(5): 509516.
31. Mostad, SB, et al. Cervical shedding of herpes simplex virus and cytomegalovirus throughout the menstrual cycle in women infected with human immunodeficiency virus type 1. American Journal of Obstetrics and Gynecology 2000; 183(4): 948955.
32. Shen, CY, et al. Cytomegalovirus excretion in pregnant and nonpregnant women. Journal of Clinical Microbiology 1993; 31(6): 16351636.
33. Stagno, S, et al. Cervical cytomegalovirus excretion in pregnant and nonpregnant women: suppression in early gestation. Journal of Infectious Disease 1975; 131(5): 522527.
34. Staras, SA, et al. Seroprevalence of cytomegalovirus infection in the United States, 1988–1994. Clinical Infectious Diseases 2006; 43(9): 11431151.
35. Dowd, JB, Aiello, AE. Socioeconomic differentials in immune response. Epidemiology 2009; 20(6): 902908.
36. Pawelec, G, et al. Cytomegalovirus and human immunosenescence. Reviews in Medical Virology 2009; 19(1): 4756.
37. Dock, JN, Effros, RB. Role of CD8T cell replicative senescence in human aging and in HIV-mediated immunosenescence. Aging and Disease 2011; 2(5): 382397.
38. Choi, J, Fauce, SR, Effros, RB. Reduced telomerase activity in human T lymphocytes exposed to cortisol. Brain, Behavior, and Immunity 2008; 22(4): 600605.
39. Trevisan, M, et al. Human cytomegalovirus productively infects adrenocortical cells and induces an early cortisol response. Journal of Cellular Physiology 2009; 221(3): 629641.
40. Bale, JF Jr., et al. Cytomegalovirus reinfection in young children. The Journal of Pediatrics 1996; 128(3): 347352.
41. Gaytant, MA, et al. Congenital cytomegalovirus infection after recurrent infection: case reports and review of the literature. European Journal of Pediatrics 2003; 162(4): 248253.
42. Novak, Z, et al. Cytomegalovirus strain diversity in seropositive women. Journal of Clinical Microbiology 2008; 46(3): 882886.
43. Colugnati, FA, et al. Incidence of cytomegalovirus infection among the general population and pregnant women in the United States. BioMed Central Infectious Diseases 2007; 7: 71.
44. Chebel, A, et al. Telomere uncapping during in vitro T-lymphocyte senescence. Aging Cell 2009; 8(1): 5264.
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Epidemiology & Infection
  • ISSN: 0950-2688
  • EISSN: 1469-4409
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