Abstract
Chronic obstructive pulmonary disease (COPD) is a frequent diagnosis in older individuals and contributor to global morbidity and mortality. Given the link between lung disease and aging, we need to understand how molecular indicators of aging relate to lung function and disease. Using data from the population-based KORA (Cooperative Health Research in the Region of Augsburg) surveys, we associated baseline epigenetic (DNA methylation) age acceleration with incident COPD and lung function. Models were adjusted for age, sex, smoking, height, weight, and baseline lung disease as appropriate. Associations were replicated in the Normative Aging Study. Of 770 KORA participants, 131 developed incident COPD over 7 years. Baseline accelerated epigenetic aging was significantly associated with incident COPD. The change in age acceleration (follow-up – baseline) was more strongly associated with COPD than baseline aging alone. The association between the change in age acceleration between baseline and follow-up and incident COPD replicated in the Normative Aging Study. Associations with spirometric lung function parameters were weaker than those with COPD, but a meta-analysis of both cohorts provide suggestive evidence of associations. Accelerated epigenetic aging, both baseline measures and changes over time, may be a risk factor for COPD and reduced lung function.
Highlights
Lung disease continues to be a primary determinant of morbidity and mortality worldwide
We use the Horvath DNA methylation age (DNAmAge) biomarker [14] to determine if accelerated epigenetic aging is related to lung function measurements and incident Chronic obstructive pulmonary disease (COPD) in two prospective, population-based cohorts
In KORA, a 5 yr difference in epigenetic age acceleration difference (EEAD) at baseline was associated with an increased risk of incident COPD, a though the magnitude of the associations was smaller than associations seen with other traits [9]
Summary
Lung disease continues to be a primary determinant of morbidity and mortality worldwide. Though lung function and lung disease are closely linked with aging [2], relatively little is known about how molecular indicators of biological age relate to lung disease and lung function. Decreased telomere length is an indicator of increased biological age, and is associated with pulmonary fibrosis and emphysema, suggesting a link between molecular biomarkers of aging and lung disease [4,5,6,7]. Relatively little is known about how lung disease and function relate to DNA methylation-derived aging biomarkers. We use the Horvath DNA methylation age (DNAmAge) biomarker [14] to determine if accelerated epigenetic aging is related to lung function measurements and incident COPD in two prospective, population-based cohorts
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