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Research Paper|Volume 12, Issue 16|pp 16539—16554

Accelerated epigenetic aging as a risk factor for chronic obstructive pulmonary disease and decreased lung function in two prospective cohort studies

Miyuki Breen1, Jamaji C. Nwanaji-Enwerem2,3,4, Stefan Karrasch5,6,7, Claudia Flexeder6, Holger Schulz6,7, Melanie Waldenberger8, Sonja Kunze8, Markus Ollert9,10, Stefan Weidinger11, Elena Colicino12, Xu Gao13, Cuicui Wang2, Jincheng Shen14, Allan C. Just12, Pantel Vokonas15, David Sparrow15, Lifang Hou16, Joel D. Schwartz2, Andrea A. Baccarelli13, Annette Peters6, Cavin K. Ward-Caviness17
  • 1Oak Ridge Institute for Science and Education (ORISE), Center for Public Health and Environmental Assessment, US Environmental Protection Agency, Chapel Hill, NC 27709, USA
  • 2Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
  • 3MD-PhD Program, Harvard Medical School, Boston, MA 02115, USA
  • 4Belfer Center for Science and International Affairs, Harvard Kennedy School of Government, Cambridge, MA 02138, USA
  • 5Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Inner Clinic, University Hospital of Munich, Ludwig-Maximilians-Universität, Munich, Germany
  • 6Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany
  • 7Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, Neuherberg, Germany
  • 8Research Unit Molecular Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany
  • 9Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg
  • 10Odense Research Center for Anaphylaxis, Department of Dermatology and Allergy Center, University of Southern Denmark, Odense, Denmark
  • 11Department of Genetic Dermatology, University of Kiel, Kiel, Germany
  • 12Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
  • 13Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY 10032, USA
  • 14Department of Population Health Sciences, University of Utah, School of Medicine, Salt Lake City, UT 84132, USA
  • 15Veterans Affairs Normative Aging Study, Veterans Affairs Boston Healthcare System, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA
  • 16Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
  • 17Center for Public Health and Environmental Assessment, US Environmental Protection Agency, Chapel Hill, NC 27709, USA
Received: April 15, 2020Accepted: July 14, 2020Published: August 3, 2020
https://doi.org/10.18632/aging.103784

Copyright © 2020 Breen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.