Skip to main content

Advertisement

SpringerLink
Log in

Associations of telomere length with risk of mortality from influenza and pneumonia in US adults: a prospective cohort study of NHANES 1999–2002

  • Original Article
  • Published:
Aging Clinical and Experimental Research Aims and scope Submit manuscript

Abstract

Background

Due to the ongoing Coronavirus disease 2019 (COVID-19) pandemic, interest has arisen to realize the relationship between telomere length (TL) and influenza and pneumonia mortality.

Aim

Our study attempted to investigate this correlation by analyzing information gathered from the National Health and Nutrition Examination Survey (NHANES) 1999–2002.

Methods

A total of 7229 participants were involved in the conducted research. We utilized Cox proportional risk model analysis to determine the hazard ratio (HR) and 95% confidence interval (CI) for TL and influenza and pneumonia mortality.

Results

During the average follow-up time of 204.10 ± 51.26 months, 33 (0.45%) participants died from influenza and pneumonia. After adjusting for multiple variables, shorter TL was associated with higher influenza–pneumonia mortality. In subgroup analyses stratified by sex, men exhibited stronger associations with influenza–pneumonia mortality than women (Model 1: HRmale: 0.014 vs HRfemale: 0.054; Model 2: HRmale: 0.082 vs HRfemale: 0.890; Model 3: HRmale: 0.072 vs HRfemale: 0.776). For subgroup analyses by visceral adiposity index (VAI), all statistically significant (P < 0.05) models displayed an inverse relationship between TL and influenza and pneumonia mortality.

Conclusions

Our research provides further proof for the connection between shorter telomeres and higher influenza–pneumonia mortality. Larger prospective researches are essential to support our results and explain the underlying mechanisms.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Data availability

All materials utilized to conduct this research are openly posted and accessible through references within the manuscript.

References

  1. Jackson ML, Phillips CH, Benoit J et al (2018) Burden of medically attended influenza infection and cases averted by vaccination—United States, 2013/14 through 2015/16 influenza seasons. Vaccine 36:467–472. https://doi.org/10.1016/j.vaccine.2017.12.014

    Article  PubMed  Google Scholar 

  2. Iuliano AD, Roguski KM, Chang HH et al (2018) Estimates of global seasonal influenza-associated respiratory mortality: a modelling study. Lancet 391:1285–1300. https://doi.org/10.1016/S0140-6736(17)33293-2

    Article  PubMed  Google Scholar 

  3. Yang W, Cummings MJ, Bakamutumaho B et al (2018) Dynamics of influenza in tropical Africa: temperature, humidity, and co-circulating (sub)types. Influenza Other Respir Viruses 12:446–456. https://doi.org/10.1111/irv.12556

    Article  PubMed  PubMed Central  Google Scholar 

  4. Kochanek KD, Murphy SL, Xu J et al (2019) Deaths: final data for 2017. Natl Vital Stat Rep 68:1–77

    PubMed  Google Scholar 

  5. Kody S, Cline A, Pereira FA (2022) Dermatological trends in emergency medicine. J Dermatolog Treat 33:1746–1748. https://doi.org/10.1080/09546634.2020.1853025

    Article  PubMed  Google Scholar 

  6. Jain S, Kamimoto L, Bramley AM et al (2009) Hospitalized patients with 2009 H1N1 influenza in the United States, April-June 2009. N Engl J Med 361:1935–1944. https://doi.org/10.1056/NEJMoa0906695

    Article  CAS  PubMed  Google Scholar 

  7. Gao H-N, Lu H-Z, Cao B et al (2013) Clinical findings in 111 cases of influenza A (H7N9) virus infection. N Engl J Med 368:2277–2285. https://doi.org/10.1056/NEJMoa1305584

    Article  CAS  PubMed  Google Scholar 

  8. Hariri LP, North CM, Shih AR et al (2021) Lung histopathology in coronavirus disease 2019 as compared with severe acute respiratory sydrome and H1N1 Influenza: a systematic review. Chest 159:73–84. https://doi.org/10.1016/j.chest.2020.09.259

    Article  CAS  PubMed  Google Scholar 

  9. Verma AA, Hora T, Jung HY et al (2021) Characteristics and outcomes of hospital admissions for COVID-19 and influenza in the Toronto area. CMAJ 193:E410–E418. https://doi.org/10.1503/cmaj.202795

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Cobb NL, Sathe NA, Duan KI et al (2021) Comparison of clinical features and outcomes in critically ill patients hospitalized with COVID-19 versus influenza. Ann Am Thorac Soc 18:632–640. https://doi.org/10.1513/AnnalsATS.202007-805OC

    Article  PubMed  PubMed Central  Google Scholar 

  11. Bernadotte A, Mikhelson VM, Spivak IM (2016) Markers of cellular senescence. Telomere shortening as a marker of cellular senescence. Aging (Albany NY) 8:3–11. https://doi.org/10.18632/aging.100871

    Article  CAS  PubMed  Google Scholar 

  12. Doksani Y (2019) The response to DNA damage at telomeric repeats and its consequences for telomere function. Genes (Basel) 10:318. https://doi.org/10.3390/genes10040318

    Article  CAS  PubMed  Google Scholar 

  13. Vaziri H, Benchimol S (1996) From telomere loss to p53 induction and activation of a DNA-damage pathway at senescence: the telomere loss/DNA damage model of cell aging. Exp Gerontol 31:295–301. https://doi.org/10.1016/0531-5565(95)02025-x

    Article  CAS  PubMed  Google Scholar 

  14. Haycock PC, Heydon EE, Kaptoge S et al (2014) Leucocyte telomere length and risk of cardiovascular disease: systematic review and meta-analysis. BMJ 349:g4227. https://doi.org/10.1136/bmj.g4227

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Zhan Y, Song C, Karlsson R et al (2015) Telomere length shortening and alzheimer disease–a mendelian randomization study. JAMA Neurol 72:1202–1203. https://doi.org/10.1001/jamaneurol.2015.1513

    Article  PubMed  Google Scholar 

  16. Cheng F, Carroll L, Joglekar MV et al (2021) Diabetes, metabolic disease, and telomere length. Lancet Diabetes Endocrinol 9:117–126. https://doi.org/10.1016/S2213-8587(20)30365-X

    Article  CAS  PubMed  Google Scholar 

  17. Xu X, Qu K, Pang Q et al (2016) Association between telomere length and survival in cancer patients: a meta-analysis and review of literature. Front Med 10:191–203. https://doi.org/10.1007/s11684-016-0450-2

    Article  PubMed  Google Scholar 

  18. De Boer RJ, Noest AJ (1998) T cell renewal rates, telomerase, and telomere length shortening. J Immunol 160:5832–5837

    Article  PubMed  Google Scholar 

  19. Cohen S, Janicki-Deverts D, Turner RB et al (2013) Association between telomere length and experimentally induced upper respiratory viral infection in healthy adults. JAMA 309:699–705. https://doi.org/10.1001/jama.2013.613

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Anderson JJ, Susser E, Arbeev KG et al (2022) Telomere-length dependent T-cell clonal expansion: a model linking ageing to COVID-19 T-cell lymphopenia and mortality. EBioMedicine 78:103978. https://doi.org/10.1016/j.ebiom.2022.103978

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Needham BL, Adler N, Gregorich S et al (2013) Socioeconomic status, health behavior, and leukocyte telomere length in the National Health and Nutrition Examination Survey, 1999–2002. Soc Sci Med 85:1–8. https://doi.org/10.1016/j.socscimed.2013.02.023

    Article  PubMed  PubMed Central  Google Scholar 

  22. Gong H, Yu Q, Yuan M et al (2022) The relationship between dietary copper intake and telomere length in hypertension. J Nutr Health Aging 26:510–514. https://doi.org/10.1007/s12603-022-1787-7

    Article  CAS  PubMed  Google Scholar 

  23. Amato MC, Giordano C (2014) Visceral adiposity index: an indicator of adipose tissue dysfunction. Int J Endocrinol 2014:730827. https://doi.org/10.1155/2014/730827

    Article  PubMed  PubMed Central  Google Scholar 

  24. Charlson ME, Pompei P, Ales KL et al (1987) A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 40:373–383. https://doi.org/10.1016/0021-9681(87)90171-8

    Article  CAS  PubMed  Google Scholar 

  25. Zhao H, Pan Y, Wang C et al (2021) The effects of metal exposures on Charlson comorbidity index using zero-inflated negative binomial regression model: NHANES 2011–2016. Biol Trace Elem Res 199:2104–2111. https://doi.org/10.1007/s12011-020-02331-4

    Article  CAS  PubMed  Google Scholar 

  26. Arnett DK, Blumenthal RS, Albert MA et al (2019) 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 140:e563–e595. https://doi.org/10.1161/CIR.0000000000000677

    Article  PubMed  PubMed Central  Google Scholar 

  27. Wang Q, Zhan Y, Pedersen NL et al (2018) Telomere Length and All-Cause Mortality: A Meta-analysis. Ageing Res Rev 48:11–20. https://doi.org/10.1016/j.arr.2018.09.002

    Article  CAS  PubMed  Google Scholar 

  28. Cawthon RM, Smith KR, O’Brien E et al (2003) Association between telomere length in blood and mortality in people aged 60 years or older. Lancet 361:393–395. https://doi.org/10.1016/S0140-6736(03)12384-7

    Article  CAS  PubMed  Google Scholar 

  29. Schneider CV, Schneider KM, Teumer A et al (2022) Association of telomere length with risk of disease and mortality. JAMA Intern Med 182:291–300. https://doi.org/10.1001/jamainternmed.2021.7804

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Fitzpatrick AL, Kronmal RA, Gardner JP et al (2007) Leukocyte telomere length and cardiovascular disease in the cardiovascular health study. Am J Epidemiol 165:14–21. https://doi.org/10.1093/aje/kwj346

    Article  PubMed  Google Scholar 

  31. Pooley KA, Bojesen SE, Weischer M et al (2013) A genome-wide association scan (GWAS) for mean telomere length within the COGS project: identified loci show little association with hormone-related cancer risk. Hum Mol Genet 22:5056–5064. https://doi.org/10.1093/hmg/ddt355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Codd V, Nelson CP, Albrecht E et al (2013) Identification of seven loci affecting mean telomere length and their association with disease. Nat Genet 45:422–427 (427e1-2). https://doi.org/10.1038/ng.2528

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Planas-Cerezales L, Arias-Salgado EG, Buendia-Roldán I et al (2019) Predictive factors and prognostic effect of telomere shortening in pulmonary fibrosis. Respirology 24:146–153. https://doi.org/10.1111/resp.13423

    Article  PubMed  Google Scholar 

  34. Kelley WJ, Zemans RL, Goldstein DR (2020) Cellular senescence: friend or foe to respiratory viral infections? Eur Respir J 56:2002708. https://doi.org/10.1183/13993003.02708-2020

    Article  PubMed  PubMed Central  Google Scholar 

  35. Ruiz A, Flores-Gonzalez J, Buendia-Roldan I et al (2021) Telomere shortening and its association with cell dysfunction in lung diseases. Int J Mol Sci 23:425. https://doi.org/10.3390/ijms23010425

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Chow RD, Majety M, Chen S (2021) The aging transcriptome and cellular landscape of the human lung in relation to SARS-CoV-2. Nat Commun 12:4. https://doi.org/10.1038/s41467-020-20323-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Álvarez D, Cárdenes N, Sellarés J et al (2017) IPF lung fibroblasts have a senescent phenotype. Am J Physiol Lung Cell Mol Physiol 313:L1164–L1173. https://doi.org/10.1152/ajplung.00220.2017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Jiang C, Liu G, Luckhardt T et al (2017) Serpine 1 induces alveolar type II cell senescence through activating p53–p21-Rb pathway in fibrotic lung disease. Aging Cell 16:1114–1124. https://doi.org/10.1111/acel.12643

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Yao C, Guan X, Carraro G et al (2021) Senescence of alveolar type 2 cells drives progressive pulmonary fibrosis. Am J Respir Crit Care Med 203:707–717. https://doi.org/10.1164/rccm.202004-1274OC

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Houssaini A, Breau M, Kebe K et al (2018) mTOR pathway activation drives lung cell senescence and emphysema. JCI Insight 3:93203. https://doi.org/10.1172/jci.insight.93203

    Article  PubMed  Google Scholar 

  41. Lv N, Zhao Y, Liu X et al (2022) Dysfunctional telomeres through mitostress-induced cGAS/STING activation to aggravate immune senescence and viral pneumonia. Aging Cell 21:e13594. https://doi.org/10.1111/acel.13594

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Gardner M, Bann D, Wiley L et al (2014) Gender and telomere length: systematic review and meta-analysis. Exp Gerontol 51:15–27. https://doi.org/10.1016/j.exger.2013.12.004

    Article  CAS  PubMed  Google Scholar 

  43. Müezzinler A, Zaineddin AK, Brenner H (2013) A systematic review of leukocyte telomere length and age in adults. Ageing Res Rev 12:509–519. https://doi.org/10.1016/j.arr.2013.01.003

    Article  CAS  PubMed  Google Scholar 

  44. Cutolo M, Montagna P, Brizzolara R et al (2009) Sex hormones modulate the effects of Leflunomide on cytokine production by cultures of differentiated monocyte/macrophages and synovial macrophages from rheumatoid arthritis patients. J Autoimmun 32:254–260. https://doi.org/10.1016/j.jaut.2009.02.016

    Article  CAS  PubMed  Google Scholar 

  45. Giefing-Kröll C, Berger P, Lepperdinger G et al (2015) How sex and age affect immune responses, susceptibility to infections, and response to vaccination. Aging Cell 14:309–321. https://doi.org/10.1111/acel.12326

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. de Jong M, Woodward M, Peters SAE (2021) Diabetes and COVID-19-related mortality in women and men in the UK biobank: comparisons with influenza/pneumonia and coronary heart disease. Diabetes Care 44:e22–e24. https://doi.org/10.2337/dc20-2378

    Article  CAS  PubMed  Google Scholar 

  47. Kalil AC, Thomas PG (2019) Influenza virus-related critical illness: pathophysiology and epidemiology. Crit Care 23:258. https://doi.org/10.1186/s13054-019-2539-x

    Article  PubMed  PubMed Central  Google Scholar 

  48. Quandelacy TM, Viboud C, Charu V et al (2014) Age- and sex-related risk factors for influenza-associated mortality in the United States between 1997–2007. Am J Epidemiol 179:156–167. https://doi.org/10.1093/aje/kwt235

    Article  PubMed  Google Scholar 

  49. Hoffmann J, Otte A, Thiele S et al (2015) Sex differences in H7N9 influenza A virus pathogenesis. Vaccine 33:6949–6954. https://doi.org/10.1016/j.vaccine.2015.08.044

    Article  CAS  PubMed  Google Scholar 

  50. Lorenzo ME, Hodgson A, Robinson DP et al (2011) Antibody responses and cross protection against lethal influenza A viruses differ between the sexes in C57BL/6 mice. Vaccine 29:9246–9255. https://doi.org/10.1016/j.vaccine.2011.09.110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. van der Plaat DA, Pereira M, Pesce G et al (2019) Age at menopause and lung function: a Mendelian randomisation study. Eur Respir J 54:1802421. https://doi.org/10.1183/13993003.02421-2018

    Article  CAS  PubMed  Google Scholar 

  52. Fan Y, Guo Y, Zhong J et al (2022) The association between visceral adiposity index and leukocyte telomere length in adults: results from National Health and Nutrition Examination Survey. Aging Clin Exp Res 34:2177–2183. https://doi.org/10.1007/s40520-022-02168-y

    Article  PubMed  Google Scholar 

  53. Kovacs EJ, Messingham KAN (2002) Influence of alcohol and gender on immune response. Alcohol Res Health 26:257–263

    PubMed  PubMed Central  Google Scholar 

  54. Shen G, Huang J-Y, Huang Y-Q et al (2020) The Relationship between telomere length and cancer mortality: data from the 1999–2002 National Healthy and Nutrition Examination Survey (NHANES). J Nutr Health Aging 24:9–15. https://doi.org/10.1007/s12603-019-1265-z

    Article  CAS  PubMed  Google Scholar 

  55. Weischer M, Bojesen SE, Nordestgaard BG (2014) Telomere shortening unrelated to smoking, body weight, physical activity, and alcohol intake: 4,576 general population individuals with repeat measurements 10 years apart. PLoS Genet 10:e1004191. https://doi.org/10.1371/journal.pgen.1004191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Liang Yingshan and Huang Peipei have contributed the same to this work.

Funding

No funds, grants, or other support was received.

Author information

Author notes

  1. Yingshan Liang and Peipei Huang have contributed equally to this work.

Authors and Affiliations

  1. Guangzhou Hospital of Integrated Traditional and Western Medicine, Guangzhou, 510800, China

    Yingshan Liang

  2. Southern Medical University, Guangzhou, 510000, Guangdong, China

    Peipei Huang

Authors
  1. Yingshan Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peipei Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yingshan Liang.

Ethics declarations

Conflict of interest

There are no personal or financial conflicts of interest to declare by the authors.

Ethical approval

Our research was conducted with the approval of the NCHS Research Ethics Review Board in conformity with the Declaration of Helsinki.

Research involving human participants

This article contains no research with human subjects conducted by any of the authors.

Informed consent

Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liang, Y., Huang, P. Associations of telomere length with risk of mortality from influenza and pneumonia in US adults: a prospective cohort study of NHANES 1999–2002. Aging Clin Exp Res 35, 3115–3125 (2023). https://doi.org/10.1007/s40520-023-02607-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40520-023-02607-4

Keywords

Search

Navigation