Shortened Telomeres in Circulating Leukocytes of Patients with Chronic Obstructive Pulmonary Disease

Abstract

RATIONALE: Telomere length is considered a marker for biological aging. Chronic obstructive pulmonary disease (COPD) may be associated with premature aging. OBJECTIVES: To test the hypothesis that patients with COPD experience accelerated telomere shortening and that inflammation is linked to this process. METHODS: We measured telomere length, using a quantitative polymerase chain reaction-based method, and plasma levels of various cytokines in 136 patients with COPD, 113 age- and sex-matched smokers, and 42 nonsmokers with normal lung function. MEASUREMENTS AND MAIN RESULTS: Median (range) telomere length ratio was significantly lower in patients with COPD (0.57 [0.23-1.18]) than in control smokers (0.79 [0.34-1.58]) or nonsmokers (0.85 [0.38-1.55]) (P < 0.001). The difference remained highly significant when using logistic regression analysis adjusted for age, sex, and tobacco exposure. Both females and males with COPD had shorter telomere length than same-sex control subjects. Telomere length was related to age in patients and control subjects but was shorter in patients than in control subjects in all age groups. No relationship was found between telomere length and tobacco exposure in patients or control subjects, with no difference between control smokers and nonsmokers. In patients with COPD, telomere length was related to PaO2 (P < 0.001) and PaCO2 (P < 0.001) but not to lung function parameters or the BODE Index. Patients with COPD also had elevated plasma levels of various cytokines, interleukin-6 correlating negatively with telomere length (P < 0.001). CONCLUSIONS: Given that in vivo telomere length reflects cellular turnover and exposure to oxidative and inflammatory damage, our data support accelerated aging in COPD.