Chest
Volume 149, Issue 1, January 2016, Pages 53-61
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Original Research: COPD
Various Mechanistic Pathways Representing the Aging Process Are Altered in COPD

This article has been presented in abstract form at the European Respiratory Society Conference, September 10, 2014, Munich, Germany.
https://doi.org/10.1378/chest.15-0645Get rights and content

Background

Accelerated aging has been proposed as a pathologic mechanism of various chronic diseases, including COPD. This concept has almost exclusively been approached by analyses of individual markers. We investigated whether COPD is associated with accelerated aging using a panel of markers representing various interconnected aspects of the aging process.

Methods

Lung function, leukocyte telomere length, lymphocyte gene expression of anti-aging (sirtuin 1, total klotho, and soluble klotho [Sklotho]), senescence (p16/21), and DNA repair (Ku70/80 and TERF2) proteins, and markers of systemic inflammation and oxidative stress were determined in 160 patients with COPD, 82 smoking subjects, and 38 never-smoking control subjects.

Results

Median levels for telomere length, Sklotho, Ku70, and sirtuin 1 gene expression were lower (respectively, 4.4, 4.6, and 4.7 kbp for telomere length; 74%, 82%, and 100% for Sklotho; 88%, 92%, and 100% for Ku70 and 70%, 92%, and 100% for sirtuin 1, all P < .05) in patients compared with the smoking and never-smoking control groups. P21 gene expression was higher in patients compared with smoking control subjects. Telomere length correlated with Ku70 gene expression (r = 0.15, P = .02). After correction for age, smoking history, systemic inflammation, and oxidative stress, telomere length and p21 were the only markers that remained independently associated with lung function. In separate groups, only telomere length remained associated with lung function parameters.

Conclusions

Markers of the aging mechanism represent distinct molecular aspects of aging. Among them, different markers were altered in COPD, but only telomere length was consistently associated with lung function, and seems a useful marker for expressing accelerated aging in COPD.

Section snippets

Study Population

As part of the Individualized COPD Evaluation in relation to Ageing (ICE-Age) study, registered on www.controlled-trails.com with identifier ISRCTN86049077, a total of 280 subjects were enrolled (Figure 1). From them, 160 clinically stable patients with COPD were randomly selected (n = 35) or admitted for pulmonary rehabilitation in CIRO (Horn, The Netherlands), and 120 healthy elderly (82 smokers and 38 never-smokers) were recruited from the same region and were of comparable sex and age to

Subject Characteristics

The patients with COPD had, as defined, significant airflow obstruction (Table 1). In addition, the PY number and number of ex-smokers was higher in patients compared with the control smokers. Plasma levels of CRP, IL-6, fibrinogen as well as total leukocyte numbers were increased and IL-8 tended to be increased in patients with COPD compared with both control groups. Plasma uric acid levels and catalase gene expression were not different, but SOD2 gene expression was significantly lower in the

Discussion

This is the first study, to our knowledge, investigating a batch of aging markers in smoker and never-smoker control subjects and subjects with COPD. Our hypothesis that all aging markers were altered in the COPD group could not be confirmed, albeit consistent alterations of different markers in circulating blood cells of patients with COPD were present. Telomere length was shorter and expression of the anti-aging molecules sirtuin 1 and Sklotho, and of the DNA repair gene Ku70 were decreased

Acknowledgments

Author contributions: E. P. A. R., P. G., E. F. M. W., and N. L. R. contributed to study conception and design; E. P. A. R., P. G., F. M. E. F., G. J. H., and N. L. R. contributed to analysis and interpretation; E. P. A. R. and N. L. R. guarantee the manuscript and are responsible for the data and its accuracy; and E. P. A. R., E. F. M. W., F. M. E. F., L. E. V., M. A. S., and N. L. R. contributed to the drafting of the manuscript for important intellectual content.

Financial/nonfinancial

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    FUNDING/SUPPORT: This study was performed by a grant of the Lung Foundation Netherlands, previously Dutch Asthma Foundation [3.2.09.049].

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