Accelerated aging in COPD : the relationship of telomere length and mortality in COPD

The evidence for the role of accelerated aging in COPD progression is growing and the senescence hypothesis is one possible molecular pathway by which COPD develops. Telomeres are used as a biomarker of cellular aging, and cellular aging is accelerated by the presence of oxidative stress and inflammation. Previous studies have shown that telomeres of peripheral blood cells are significantly shorter in COPD patients, but no studies to date explored the relationship of telomere length to important health outcomes such as mortality. Using samples from Lung Health Study (LHS), we examined the role of telomere length and polymorphisms in genes involved in aging process in health outcomes in COPD patients. There were no significant differences in age, sex, BMI, race of cumulative smoking exposure (pack-years) among 4 groups, divided on basis of telomere length. However, the risk of all cause mortality was similar across the first 3 quartiles (short telomere) but dropped significantly in the 4th quartile (longest telomere, hazard ratio (HR), 1.30). Compared to individuals in the 4th quartile of relative telomere length, the remaining participants had significantly higher risk of cancer mortality (HR, 1.48). Smoking status did not make a significant difference in leukocyte telomere length but when compared to non-COPD, age matched control group, all smoker groups in LHS had shorter telomeres. We also investigated the role of SNPs that were previously associated with leukocyte telomere length in disease outcome. Although no SNPs were associated with leukocyte telomere length, several SNPs of telomere biology genes were associated with cardiovascular and lung cancer mortality. The rate of telomere attrition is influenced by both extrinsic factors, such as inflammation and oxidative stress and intrinsic factors such as genetic predisposition. Here, we have shown that accelerated aging of peripheral blood cells, indicated by short telomeres, seems to play a role in disease outcome of COPD. Although we failed to show significant associations between leukocyte telomere length and genetic polymorphisms of telomere regulatory genes, the SNPs may contribute to risk of mortality. Further research is needed to elucidate the pathways underlying these observations.Medicine, Faculty ofMedicine, Department ofExperimental Medicine, Division ofGraduat