Younger epigenetic age is associated with higher cardiorespiratory fitness in individuals with airflow limitation

We hypothesized that increased cardiorespiratory fitness (CRF) slows down a person’s aging, particularly in individuals with chronic airflow limitation (CAL). Participants aged ≥40 years (n = 78) had baseline blood DNA methylation profiled and underwent cardiopulmonary cycle exercise testing at baseline and at three years. Epigenetic clocks were calculated and tested for their association with CRF using linear regression. Differentially methylated genes associated with CRF were identified using a robust linear model. Higher CRF at baseline was associated with lower age acceleration in the epigenetic clocks DNAmAgeSkinBlood (p = 0.016), DNAmGrimAge (p = 0.012), and DNAmGrimAge2 (p = 0.011). These effects were consistent in individuals with CAL (DNAmGrimAge p = 0.009 and DNAmGrimAge2 p = 0.007). CRF at three years was associated with baseline DNAmGrimAge (p = 0.015) and DNAmGrimAge2 (p = 0.011). Differentially methylated genes associated with CRF enriched multiple aging-related pathways, including cellular senescence. Enhancing CRF may be one intervention that can slow biological aging and improve health outcomes in chronic respiratory diseases. [Display omitted] •Younger epigenetic age is associated with cardiorespiratory fitness in airflow obstruction•Self-reported activity and VO2 tests confirm the link between fitness and aging•Cardiorespiratory fitness impacts DNA methylation along aging-related pathways Cardiovascular medicine; Kinesiology; Respiratory medicine