LSC - 2024 - Epigenetic age acceleration and severity of airflow limitation on blood and lung tissue of COPD

<bold>Background:</bold> Accelerated lung ageing has been proposed as a mechanism of chronic obstructive lung disease (COPD). Yet, whether the aging markers in lung tissue and blood in COPD patients are similar or if they change with the severity of airflow limitation is unclear. This study sought to explore these questions using DNA methylation-based aging calculation algorithms (i.e. epigenetic clocks), previously developed to measure the biological age of a variety of tissues. <bold>Methods:</bold> DNA was extracted from blood (n=168) and lung tissue (n=138) of COPD patients with different degrees of airflow limitation severity (FEV1% ref.). Genome wide DNA methylation was assessed with EPIC arrays (Illumina), and the biological age and age acceleration was computed with 7 epigenetic clocks, and with the mDNA-TL estimator (a Telomere length shortening measure). Multivariable linear regressions adjusted for chronological age, sex, pack-year and smoking status, were used for the analysis. <bold>Results:</bold> In blood, airflow limitation severity was associated with the biological age acceleration determined by three epigenetic clocks (BLUP, Levine, DunedinPACE) and by the mDNA-TL estimator. By contrast, in lung tissue only the mDNA-TL estimator showed a significant association with the severity of airflow limitation. <bold>Conclusions:</bold> COPD patients with more severe airflow limitation present a higher biological epigenetic age acceleration only in blood. However, both blood and lung tissue of these patients present an accelerated Telomere shortening. These findings suggest that the pace of aging biomarkers is different in the two tissues.