Abstract
Rationale: COPD has been associated with accelerated ageing. Since COPD is a heterogeneous disease in terms of systemic inflammation and oxidative stress, it remains to be investigated whether COPD per se or its systemic manifestations are associated with ageing.
Methods: 160 COPD patients, 79 smoking and 41 never smoking age-matched control subjects had assessment of lung function, systemic inflammation (plasma CRP, fibrinogen, leukocytes, Il-6 levels) and oxidative stress (plasma uric acid level and SOD gene expression). Telomere length and Ku70 gene expression, an enzyme regulating telomere length were determined in PBMC and lymphocytes respectively.
Results: The COPD group was characterized by systemic inflammation and oxidative stress. Telomere length was lower in the patients compared to both the smoking and non-smoking control groups (4.3(4.0-4.7) vs. 4.6(4.2-5.2)* vs. 4.6(4.1-5.1)* kilo base pairs respectively, *p<0.05 vs. COPD), indicating that cellular age of a COPD patient is ∼7.5 years older than a control subject of the same age. Telomere length correlated with FEV1/FVC (r=0.25, p<0.01), leukocytes (r=-0.23, p<0.01) and uric acid (r=0.11, p=0.06) in the total group. After correction for confounders, telomere length was associated with age and FEV1/FVC in the total group (β=0.24, p<0.01) and the control group (β=0.24, p<0.01). In the total group, telomere length was independently associated with Ku70 gene expression (β=0.12, p=0.05).
Conclusion: The present study provides evidence that COPD is associated with accelerated cellular ageing. Despite the absence of a relation with systemic manifestations, this study suggests a mechanistic link with Ku70 gene expression.
- © 2014 ERS