The role of telomere shortening in the development and progression of COPD

Abstract

The prevalence and incidence of COPD increase with age in all populations studied. These associations suggest that normal aging could contribute to the pathogenesis of COPD. Telomeres are DNA structures at the end of chromosomes which protect DNA from degradation and unneeded recombination events. Telomere length decreases with age. At a critical length cells undergo senescence which results in changes in cell morphology, gene activity, and cytokine production. Senescent cells eventually undergo programmed cell death (apoptosis) and drop out of tissue structures. Telomeres from lung tissue and circulating leukocytes are shorter in patients with COPD. Lung biopsy specimens indicate that patients with COPD have increased numbers of apoptotic epithelial and endothelial cells. This information suggests that normal aging or accelerated aging or senescence induced by oxidant injury and/or inflammation contributes to the development of COPD. Longitudinal studies suggest that patients with shorter telomere have increased all cause and cancer mortality. Therefore, telomere attrition is associated with important consequences in these patients. In addition, animal studies suggest that patients with shorter telomeres are at increased risk of developing COPD. These observations raise the possibility that drugs designed to increase telomere length or to prevent telomere attrition might slow the progression of COPD. However, very careful studies with animal models of COPD and of malignancy are needed to determine benefits and to make certain that this genetic manipulation does not increase the risk of malignancy.