The relationship between the epigenetic aging biomarker “grimage” and lung function in both the airway and blood of people living with HIV: An observational cohort study

BACKGROUND: Age-related comorbidities such as chronic obstructive pulmonary disease (COPD) are common in people living with human immunodeficiency virus (PLWH). We investigated the relationship between COPD and the epigenetic age of the airway epithelium and peripheral blood of PLWH. METHODS: Airway epithelial brushings from 34 PLWH enrolled in the St. Paul's Hospital HIV Bronchoscopy cohort and peripheral blood from 378 PLWH enrolled in The Strategic Timing of Antiretroviral Treatment (START) study were profiled for DNA methylation. The DNA methylation biomarker of age and healthspan, GrimAge, was calculated in both tissue compartments. We tested the association of GrimAge with COPD in the airway epithelium and airflow obstruction as defined by an FEV(1)/FVC<0.70, and FEV(1) decline over 6 years in blood. FINDINGS: The airway epithelium of PLWH with COPD was associated with greater GrimAge residuals compared to PLWH without COPD (Beta=3.18, 95%CI=1.06-5.31, P=0.005). In blood, FEV(1)/FVC<LLN was associated with greater GrimAge residuals (Beta=1.74, 95%CI=0.37-3.24, P=0.019). FEV(1) decline was inversely correlated with GrimAge residuals in blood (r=−0.13, P=0.012). PLWH who had normal lung function but who subsequently developed an FEV(1)/FVC<0.70 over the course of 6 years had higher GrimAge residuals at baseline (Beta=2.33, 95%CI=0.23-4.44, P=0.031). INTERPRETATION: GrimAge may reflect lung and systemic epigenetic changes that occur with advanced airflow obstruction and may help to identify PLWH with a higher risk of developing COPD. FUNDING: Canadian Institutes of Health Research and the British Columbia Lung Association. The START substudy was funded by NIH grants: UM1-AI068641, UM1-AI120197, and RO1HL096453.