Abstract
Study design
Cross-sectional study
Objectives
To determine clinical factors associated with telomere length in persons with chronic spinal cord injury (SCI).
Setting
Veterans Affairs Medical Center, Boston, MA.
Methods
Two hundred seventy-eight participants with chronic SCI provided blood samples for measurement of C-reactive protein (CRP), interleukin-6 (IL-6), and telomere length, completed respiratory health questionnaires, underwent dual X-ray absorptiometry (DXA) to assess body fat, and completed spirometry. High-throughput real-time PCR assays were used to assess telomere length in leukocyte genomic DNA. Linear regression models were used to assess cross-sectional associations with telomere length.
Results
Telomere length was inversely related to age (p < 0.0001). In age-adjusted models, gender, race, injury duration, %-total and %-trunk fat, body mass index (BMI), %-predicted forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1), chronic cough or phlegm, CRP, IL-6, wheeze, smoking, diabetes, heart disease, chronic obstructive pulmonary disease (COPD), skin ulcer, urinary tract infection (UTI), or chest illness history were not significantly associated with telomere length. There was a suggestive age-adjusted association between persons with the most severe SCI (cervical motor complete and AIS C) and shorter telomere length (p = 0.055), an effect equivalent to ~8.4 years of premature aging. There were similar age-adjusted associations with telomere length between persons using a wheelchair (p = 0.059) and persons with chronic urinary catheter use (p = 0.082) compared to persons without these characteristics.
Conclusions
Our results suggest that clinical characteristics such as decreased mobility and bladder dysfunction that are common in individuals with more severe SCI are associated with shorter telomere length.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Data availability
The data for this study are archived at VA Boston Healthcare System and are not publicly available per Department of Veterans Affairs information privacy rules.
Change history
15 January 2020
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
References
Aubert G, Lansdorp PM. Telomeres and aging. Physiol Rev. 2008;88:557–79.
Fasching CL. Telomere length measurement as a clinical biomarker of aging and disease. Crit Rev Clin Lab Sci. 2018;55:443–65.
Mui TS, Man J, McElheney J, Sandford A, Coxson H, Birmingham C, et al. Telomere length and chronic obstructive pulmonary disease: evidence of accelerated aging. J Am Geriatr Soc. 2009;57:2372–4.
Guan JZ, Guan WP, Maeda T, Guoqing X, GuangZhi W, Makino N. Patients with multiple sclerosis show increased oxidative stress markers and somatic telomere length shortening. Mol Cell Biochem. 2015;400:183–7.
Steer SE, Williams FMK, Kato B, Gardner JP, Norman PJ, Hall MA, et al. Reduced telomere length in rheumatoid arthritis is independent of disease activity and duration. Ann Rheum Dis; Lond. 2007;66:476.
Willeit P, Willeit J, Mayr A, et al. Telomere length and risk of incident cancer and cancer mortality. JAMA. 2010;304:69–75.
Astuti Y, Wardhana A, Watkins J, Wulaningsih W, PILAR Research Network. Cigarette smoking and telomere length: a systematic review of 84 studies and meta-analysis. Environ Res. 2017;158:480–9.
Mundstock E, Sarria EE, Zatti H, Louzada FM, Grun LK, Jones MH, et al. Effect of obesity on telomere length: systematic review and meta-analysis. Obesity. 2015;23:2165–74.
Garshick E, Kelley A, Cohen SA, Garrison A, Tun CG, Gagnon D, et al. A prospective assessment of mortality in chronic spinal cord injury. Spinal Cord. 2005;43:408–16.
Goldstein RL, Walia P, Teylan M, Lazzari AA, Tun CG, Hart JE, et al. Clinical factors associated with C-reactive protein in chronic spinal cord injury. Spinal Cord. 2017;55:1088–95.
Garshick E, Walia P, Goldstein RL, Teylan MA, Lazzari AA, Tun CG, et al. Associations between vitamin D and pulmonary function in chronic spinal cord injury. J Spinal Cord Med. 2019;42:171–7.
Walia P, Goldstein RL, Teylan M, Lazzari AA, Hart JE, Tun CG, et al. Associations between vitamin D, adiposity, and respiratory symptoms in chronic spinal cord injury. J Spinal Cord Med. 2018;41:667–75.
Kirshblum SC, Waring W, Biering-Sorensen F, Burns SP, Johansen M, Schmidt-Read M, et al. Reference for the 2011 revision of the International Standards for Neurological Classification of Spinal Cord Injury. J Spinal Cord Med. 2011;34:547–54.
Zariffa J, Kramer JLK, Jones LAT, Lammertse DP, Curt A, Steeves JD, European Multicenter Study about Spinal Cord Injury (EMSCI) Study Group. Sacral Sparing in SCI: beyond the S4–S5 and Anorectal Examination. Spine J. 2012;12:389–400.
Hart JE, Goldstein R, Walia P, Teylan M, Lazzari A, Tun CG, et al. FEV1 and FVC and systemic inflammation in a spinal cord injury cohort. BMC Pulm Med. 2017;17:113.
Ferris BG. Epidemiology Standardization Project (American Thoracic Society). Am Rev Respir Dis. 1978;118(6 Pt 2):1–120.
Cawthon RM. Telomere measurement by quantitative PCR. Nucleic Acids Res. 2002;30:e47.
Willeit P, Willeit J, Kloss-Brandstätter A, Kronenberg F, Kiechl S. Fifteen-year follow-up of association between telomere length and incident cancer and cancer mortality. JAMA. 2011;306:42–4.
Wong LSM, Boer RA, de Samani NJ, Veldhuisen DJ, van Harst P. Telomere biology in heart failure. Eur J Heart Fail. 2008;10:1049–56.
Jin X, Pan B, Dang X, Wu H, Xu D. Relationship between short telomere length and stroke: a meta-analysis. Med (Baltim). 2018;97:e12489.
Ornish D, Lin J, Chan JM, Epel E, Kemp C, Weidner G, et al. Effect of comprehensive lifestyle changes on telomerase activity and telomere length in men with biopsy-proven low-risk prostate cancer: 5-year follow-up of a descriptive pilot study. Lancet Oncol. 2013;14:1112–20.
Balan E, Decottignies A, Deldicque L. Physical activity and nutrition: two promising strategies for telomere maintenance? Nutrients. 2018;10:1942.
Sun X, Jones ZB, Chen X, Zhou L, So K-F, Ren Y. Multiple organ dysfunction and systemic inflammation after spinal cord injury: a complex relationship. J Neuroinflamm. 2016;13:260.
Ho C-H, Sung K-C, Lim S-W, Liao C-H, Liang F-W, Wang J-J, et al. Chronic indwelling urinary catheter increase the risk of bladder cancer, even in patients without spinal cord injury. Med (Baltim). 2015;94:e1736.
Wong JYY, Vivo ID, Lin X, Fang SC, Christiani DC. The relationship between inflammatory biomarkers and telomere length in an occupational prospective cohort study. PLoS ONE. 2014;9:e87348.
Pedroso DCC, Miranda-Furtado CL, Kogure GS, Meola J, Okuka M, Silva C, et al. Inflammatory biomarkers and telomere length in women with polycystic ovary syndrome. Fertil Steril. 2015;103:542–7.e2.
Sergio LP, da S, Paoli F, de, Mencalha AL, Da, Fonseca AS. Chronic obstructive pulmonary disease: from injury to genomic stability. J Chronic Obstr Pulm Dis. 2017;14:439–50.
Cordoba-Lanus E, Espinoza-Jimenez A, Baz-Davila R, Cazorla S, Montejo-de-Garcini A, Aguirre-Jaime A, et al. Telomere shortening and progression in patients with chronic obstructive pulmonary disease (COPD). Am J Respir Crit Care Med. 2016;193:A2340.
Andujar P, Courbon D, Bizard E, Marcos E, Adnot S, Boyer L, et al. Smoking, telomere length and lung function decline: a longitudinal population-based study. Thorax 2018; 73:283–5.
Desai K, Berkman N, Cohen-Manheim I, Sinnreich R, Aviv A, Kark JD. Rapid shortening of leukocyte telomeres is associated with poorer pulmonary function among healthy adults. Respir Med. 2018;145:73–9.
Rode L, Bojesen SE, Weischer M, Vestbo J, Nordestgaard BG. Short telomere length, lung function and chronic obstructive pulmonary disease in 46 396 individuals. Thorax. 2013;68:429–35.
Tellechea ML, Pirola CJ. The impact of hypertension on leukocyte telomere length: a systematic review and meta-analysis of human studies. J Hum Hypertens. 2017;31:99.
Murillo-Ortiz B, Albarrán-Tamayo F, Arenas-Aranda D, Benítez-Bribiesca L, Malacara-Hernández JM, Martínez-Garza S, et al. Telomere length and type 2 diabetes in males, a premature aging syndrome. Aging Male. 2012;15:54–8.
Zhao J, Miao K, Wang H, Ding H, Wang DW. Association between telomere length and type 2 diabetes mellitus: a meta-analysis. PLoS ONE. 2013;8:1–4.
Acknowledgements
We thank Antonio A. Lazzari, MD, CCD, PhD and Samuel Davis, Boston VA Healthcare System, technician, for DXA data collection. We appreciate the participation of Veterans at VA Boston and others from the greater Boston area with chronic SCI.
Funding
This study was supported by VA Rehabilitation Research and Development Merit Review Grants B6618R, I01RX000792, and I01RX000596 from the U.S. Department of Veterans Affairs Rehabilitation Research and Development Service and NIH NIAMS Grant R01AR059270. The contents do not represent the views of the U.S. Department of Veterans Affairs or the United States Government. Presented in part in abstract form at the American Thoracic Society International Conference, San Diego in 2014.
Author information
Authors and Affiliations
Contributions
EG, ID, and JEH contributed to study conception and design. MT, RLG, EO, EG, and DMM were responsible for data analysis with review and interpretation by ID and JEH. DMM, RLG, and EG were responsible for the draft manuscript. All authors contributed to editing and approved the final manuscript.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Statement of ethics
The Institutional Review Board at VA Boston Healthcare System approved the protocol (IRB #2609). We certify that all applicable institutional and governmental regulations concerning the ethical use of human volunteers were followed during the course of this research.
Informed consent
Informed written consent was obtained from all volunteers who participated in this study.
Additional information
Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Monroe, D.M., Goldstein, R.L., Teylan, M.A. et al. Clinical associations with telomere length in chronic spinal cord injury. Spinal Cord 57, 1084–1093 (2019). https://doi.org/10.1038/s41393-019-0336-7
Received:
Revised:
Accepted:
Published:
Version of record:
Issue date:
DOI: https://doi.org/10.1038/s41393-019-0336-7
