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

Abstract

Several clinical studies suggest the involvement of premature ageing processes in chronic obstructive pulmonary disease (COPD). Using an epidemiological approach, we studied whether accelerated ageing indicated by telomere length, a marker of biological age, is associated with COPD and asthma, and whether intrinsic age-related processes contribute to the interindividual variability of lung function.Our meta-analysis of 14 studies included 934 COPD cases with 15 846 controls defined according to the Global Lungs Initiative (GLI) criteria (or 1189 COPD cases according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria), 2834 asthma cases with 28 195 controls, and spirometric parameters (forced expiratory volume in 1 s (FEV1), forced vital capacity (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 asthma (b5 -0.0452, p50.024) as well as COPD (b5 -0.0982, p50.001), with associations being stronger and more significant when using GLI criteria than those of GOLD. In both diseases, effects were stronger in females than males. The investigation of spirometric indices showed positive associations between telomere length and FEV1 (p51.07610 -7 ), FVC (p52.07610 -5 ), and FEV1/FVC (p55.27610 -3 ). The effect was somewhat weaker in apparently healthy subjects than in 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 ageing primarily due to intrinsic processes, which are likely to be aggravated in lung diseases. @ERSpublicationsTelomere length is decreased in asthma and COPD patients and positively associated with spirometric indices

Genetic and Environmental Effects on Telomere Length and Lung Function: A Twin Study

“…Our data suggest for the first time, that in spite of the associations observed in other studies and our team (7,8) …”

“…The association observed between LTL and lung function in the present and earlier papers (7,8) suggests the presence of common factors involving both the telomere biology and lung function. Of the potential unique environmental factors, tobacco smoke is known to promote aging processes and cellular senescence (38) and telomere shortening (8) in addition to its known damaging effects on lung function (39).…”

“…Another possible shared factor is chronic inflammation, which is known to increase with aging. We have previously reported stronger associations between LTL and lung function among asthmatics and COPD patients than lung-healthy subjects (7). It is possible that LTL and lung function are somehow related through intrinsic age-related processes which are aggravated by, for example, chronic inflammation either locally in the lung tissue or systemically in the whole body.…”

“…However, this association is typically reported to be small and dependent of several health related habits and existence and progress of chronic diseases. COPD patients, asthmatics and smokers have shorter telomeres than healthy, non-smoking subjects (7)(8)(9). The associations found between LTL and lung function have led researchers to hypothesize that lung function may serve as a surrogate marker for biological aging, which is aggravated in lung diseases, possibly owing to intrinsic aging processes (7), oxidative stress and chronic inflammation (10).…”

Telomerase and the Genetics of Emphysema Susceptibility. Implications for Pathogenesis Paradigms and Patient Care

“…A few studies have examined telomere length in populations of patients with COPD. They have consistently documented a reproducible shortening of telomere length in COPD, but the effect size was variable, and these studies did not examine extreme COPD phenotypes (42)(43)(44)(45). The recent discoveries indicate that telomere shortening, within certain abnormal thresholds relative to healthy populations, plays a causal role in mediating susceptibility.…”