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A2400 - Epigenetic Age Acceleration and Lung Function Decline in the Normative Aging Study
Author Block: J. M. Lee1, S. G. Rasmussen2, K. Brennan2, E. Colicino3, A. C. Just3, P. Vokonas4, X. Lin5, L. Hou6, A. A. Litonjua7, D. L. DeMeo8, D. Sparrow9, J. Schwartz10, A. Baccarelli11; 1Pulmonary, Allergy and Critical Care Medicine, Columbia University Medical Center, New York, NY, United States, 2Columbia University Mailman School of Public Health, New York, NY, United States, 3Icahn School of Medicine at Mount Sinai, New York, NY, United States, 4VA Normative Aging Study, VA Boston Healthcare System, Boston University School of Public Health, Boston, MA, United States, 5Harvard T.H. Chan School of Public Health, Boston, MA, United States, 6Feinberg School of Medicine Northwestern University, Chicago, IL, United States, 7University of Rochester Medical Center, Rochester, NY, United States, 8Brigham and Womens Hosp, Boston, MA, United States, 9VA Normative Aging Study, VA Boston Healthcare System, Boston University School of Public Health, Boston, NY, United States, 10Dept of Envir Hlth/Dept of Epidem, Harvard Sch of Public Health, Boston, MA, United States, 11Environmental Health Sciences, Columbia University, New York, NY, United States.
Rationale: Epigenetic age is based on DNA methylation changes at 353 CpG sites on the human genome and acts as a tissue-independent predictor of biologic age. Prior studies have shown that epigenetic age acceleration, defined as epigenetic age minus chronologic age, is associated with age-related diseases including cognitive decline, cancer, and frailty. There has been little research examining the relationship between epigenetic age and lung function. The aim of this study is to assess whether epigenetic age is associated with lung function change among older individuals.
Methods: We analyzed participants from the US Department of Veterans Affairs Normative Aging Study (NAS) who had blood DNA methylation and spirometry testing between 1999 - 2012. Participants provided a baseline blood DNA methylation sample and information about medication use, pulmonary disorders and smoking history. Participants performed spirometry at baseline and at a subsequent visit. Blood DNA methylation was processed using the Illumina HumanMethylation 450BeadChips. Epigenetic age was calculated through Horvath’s publically available online calculator. Spirometric tests were performed according to American Thoracic Society guidelines. Testing was performed by trained technicians and a minimum of three acceptable spirograms was obtained, of which at least two were reproducible within 5% of both forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). Multiple linear regression was used to examine the relationship between epigenetic age acceleration and changes in FEV1 and FVC. Results: Epigenetic age and spirometry data were available for 363 participants. After statistical testing for outliers of the predictor, we included 351 participants. All participants were white men residing in New England. Baseline characteristics included a mean age of 72 years (range 55-100), 68% were current or former smokers, 9% had asthma, and 9% had COPD. The mean time to subsequent spirometry testing was 4.5 years. Regression modelling showed statistically significant associations between epigenetic age acceleration and declines in FEV1 (p=0.027) and FVC (p=0.016) when adjusting for height, weight, time interval between spirometry testing, smoking status, education level, asthma, COPD, folate intake and white cell counts.
Conclusion: Epigenetic age acceleration is associated with declines in FEV1 and FVC. Epigenetic age measurement could be a potential biomarker for assessing and managing at-risk populations for accelerated pulmonary function decline.