Telomere length in circulating leukocytes is associated with lung function and disease

Abstract

Several clinical studies suggest the involvement of premature aging processes in COPD. Using an epidemiological approach we studied whether accelerated aging indicated by telomere length, a marker of biological age, is associated with COPD and asthma, and whether intrinsic age-related processes contribute to the inter-individual variability of lung function. Our meta-analysis of 14 studies included 934 COPD cases with 15,846 controls defined according to GLI criteria (or 1,189 COPD cases according to GOLD), 2,834 asthma cases with 28,195 controls, and spirometric parameters (FEV1, FVC and FEV1/FVC) of 12,595 individuals. Associations with telomere length were tested by linear regression, adjusting for age, sex, and smoking status.We observed negative associations between telomere length and COPD being stronger for COPD defined by GLI than GOLD (β=-0.0982, p=0.001 vs. β=-0.0676, p=0.018) as well as asthma (β=-0.0452, p=0.024), with stronger effects in women compared to men. The investigation of spirometric indices showed positive associations between telomere length and FEV1 (p=1.07x10-7), FVC (p=2.07x10-5), and their ratio FEV1/FVC (p=5.27x10-3). The effect was somewhat weaker in apparently healthy subjects compared to COPD or asthma patients. Our results provide indirect evidence for the hypothesis that cellular senescence may contribute to the pathogenesis of COPD and asthma and that lung function may reflect biological aging primarily due to intrinsic processes which are likely to be aggravated in lung diseases.