Accelerated epigenetic age in Bronchiectasis

Background: Patients with severe bronchiectasis (BQ), as determined by the Bronchiectasis Severity Index (BSI), have a specific epigenetic signature (CpG methylations). Here we explored if the BE altered methylation signature is associated with accelerated cell ageing using five epigenetic clocks. Clocks are a series of studied patterns in cpg methylation sites that estimate biological age. Methods: DNA was extracted from blood of BQ patients (n=91) with a range of BSI values. DNA methylation was assessed using the EPIC array (Illumina). The Hovarth, Hannum, PhenoAge, GrimAge and DuneinPACE epigenetic clocks were used to determine the epigenetic age acceleration in each patient. Linear regression models, adjusted for sex and smoking were used to explore the association of the epigenetic age acceleration measured by each clock with the BSI value and the severity of airflow limitation (FEV1% ref.). Age acceleration was also compared between patients with and without chronic P. Aeruginosa (PA) airway colonization. Results: Age acceleration determined with PhenoAge p= 0.031, GrimAge p= 9.07E-05 and DuneinPACE p= 7.13E-09 but not with Hovarth, Hannum (first generation clocks) was significantly associated to BSI. Age acceleration measured by GrimAge and DunedinPACE differed between patients with and without PA. Conclusion: The second and third generation epigenetic clocks PhenoAge, GrimAge and DuneinPACE identify accelerated ageing in patients with severe BQ, and in those with PA colonization. These findings open a new perspective in patients with BQ, linking epigenetics signature with known morbimortality factors Supported by Instituto de Salud Carlos III (PI21/00419, CD23/00093), FEDER Funds, SEPAR, FUCAP, ICREA and Serra Húnter Program.