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Accelerated Epigenetic Aging as a Risk Factor for Chronic Obstructive Pulmonary Disease and Decreased Lung Function in two Prospective Cohort Studies

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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.

Impact/Purpose

Using data from the Cooperative Health Research in the Region of Augsburg surveys, we examined associations between DNA methylation-derived biomarkers of aging and measures of lung function and incident lung disease (asthma and chronic obstructive pulmonary disorder [COPD]). We examined associations with baseline DNA methylation age acceleration as well as with the change in age acceleration between baseline and follow-up. All lung function and incident disease outcomes were assessed at follow-up while aging biomarkers and all covariates (age, sex, height, and weight) were measured at baseline. Conclusion: Accelerated epigenetic aging may be an independent risk factor for incident COPD. Given the links between epigenetic aging and both inflammation and environmental exposures, there are multiple mechanisms that may explain these associations. Using data from the population-based KORA (Cooperative Health Research in the Region of Augsburg) surveys, we examined associations of DNA methylation-derived biomarkers of aging with spirometric indices and incident lung disease (asthma and chronic obstructive pulmonary disease [COPD]). We examined associations with baseline DNA methylation age acceleration as well as with the change in age acceleration between baseline and follow-up. All spirometric and incident disease outcomes were assessed at follow-up while aging biomarkers and all covariates (age, sex, height, and weight) were measured at baseline. Associations were replicated in the USA based Normative Aging Study. Results: There were 1,473 KORA participants with data available at follow-up, 130 of whom had incident COPD and 52 of whom had incident asthma. Accelerated aging was significantly associated with incident COPD and with a combined outcome of incident COPD + asthma. The change in age acceleration between baseline and follow-up was even more strongly associated with lung disease than baseline aging alone. We replicated associations between the change in age acceleration between baseline and follow-up and incident COPD in the Normative Aging Study, a cohort of older males. Associations with spirometric parameters were weak, but consistently suggested that accelerated aging may be associated with decreased lung function, and associations strengthened in a meta-analysis of both cohorts. Conclusion: Accelerated epigenetic aging may be an independent risk factor for incident COPD and decreased lung function. Given the links between epigenetic aging and both inflammation and environmental exposures, there are multiple mechanisms that may explain these associations.

Citation

Breen, M., J. Nwanaji-Enwerem, S. Karrasch, C. Flexeder, H. Schulz, M. Waldenberger, S. Kunze, M. Ollert, S. Weidinger, E. Colicino, X. Gao, C. Wang, J. Shen, A. Just, P. Vokonas, L. Hou, J. Schwartz, A. Baccarelli, A. Peters, C. Ward-Caviness, AND D. Sparrow. Accelerated Epigenetic Aging as a Risk Factor for Chronic Obstructive Pulmonary Disease and Decreased Lung Function in two Prospective Cohort Studies. Impact Journals, LLC, Orchard Park, NY, 12(16):16539-16554, (2020). [DOI: 10.18632/aging.103784]

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DOI: Accelerated Epigenetic Aging as a Risk Factor for Chronic Obstructive Pulmonary Disease and Decreased Lung Function in two Prospective Cohort Studies
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Last updated on December 09, 2020
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