TY - JOUR T1 - LSC 2013 abstract - Pulmonary senescence in chronic obstructive pulmonary disease is primarily mediated by persistent DNA double strand breaks JF - European Respiratory Journal JO - Eur Respir J VL - 42 IS - Suppl 57 SP - PP167 AU - Manish Kumar AU - Nobert Weissman AU - Werner Seeger AU - Robert Voswinckel Y1 - 2013/09/01 UR - http://erj.ersjournals.com/content/42/Suppl_57/PP167.abstract N2 - Introduction: Chronic obstructive pulmonary disease or COPD is an age associated disease that occurs after a prolonged period of cigarette smoking. Deregulated repair, tissue degeneration and lung regression are the hallmarks of COPD. Cellular senescence is a signal transduction program leading to irreversible cell cycle arrest. The growth arrest can be triggered by many different mechanisms including recognition by cellular sensors of DNA double-strand breaks leading to the activation of cell cycle checkpoint responses and recruitment of DNA repair foci. We propose COPD to be a disease of premature lung senescence and aim to decipher markers of DNA damage, repair and senescence in animal models of smoke induced emphysema as well as in smokers with and without COPD.Results: Cellular senescence could be successfully assessed by staining for β-galactosidase and evaluation of senescence associated heterochromatin foci (SAHF), reflecting condensed chromatin, in the nuclei. DNA double strand breaks and cell cycle arrest could be demonstrated by up regulated 53-BP1, γH2AX and p21.In vitro, senescence of lung fibroblasts could be induced by 100uM H2O2 as well as by 1% cigarette smoke extract. PBMC derived Circulating fibrocytes were rather stimulated in growth by H2O2 than driven towards senescence.Paraffin lung sections from Smoked Mice and Human COPD samples were investigated for markers of senescence, DNA damage and repair. Our results indicate that the senescence in case of COPD is primarily driven by the persistent DNA double-strand breaks due to prolonged cigarette smoking. ER -