Jamaji C Nwanaji-Enwerem1, Lingzhen Dai2, Elena Colicino3, Youssef Oulhote2, Qian Di2, Itai Kloog4, Allan C Just5, Lifang Hou6, Pantel Vokonas7, Andrea A Baccarelli3, Marc G Weisskopf2, Joel D Schwartz2. 1. Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA. Electronic address: jnwanajienwerem@g.harvard.edu. 2. Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 3. Department of Environmental Health Sciences, Columbia Mailman School of Public Health, New York, NY, USA. 4. Department of Geography and Environmental Development, Ben-Gurion University of the Negev, Beer Sheva, Israel. 5. Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 6. Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. 7. VA Normative Aging Study, Veterans Affairs Boston Healthcare System, The Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
Abstract
BACKGROUND: Long-term PM2.5 exposure and aging have been implicated in multiple shared diseases; studying their relationship is a promising strategy to further understand the adverse impact of PM2.5 on human health. OBJECTIVE: We assessed the relationship of major PM2.5 component species (ammonium, elemental carbon, organic carbon, nitrate, and sulfate) with Horvath and Hannum DNA methylation (DNAm) age, two DNA methylation-based predictors of chronological age. METHODS: This analysis included 552 participants from the Normative Aging Study with multiple visits between 2000 and 2011 (n=940 visits). We estimated 1-year PM2.5 species levels at participants' addresses using the GEOS-chem transport model. Blood DNAm-age was calculated using CpG sites on the Illumina HumanMethylation450 BeadChip. We fit linear mixed-effects models, controlling for PM2.5 mass and lifestyle/environmental factors as fixed effects, with the adaptive LASSO penalty to identify PM2.5 species associated with DNAm-age. RESULTS: Sulfate and ammonium were selected by the LASSO in the Horvath DNAm-age models. In a fully-adjusted multiple-species model, interquartile range increases in both 1-year sulfate (95%CI: 0.28, 0.74, P<0.0001) and ammonium (95%CI: 0.02, 0.70, P=0.04) levels were associated with at least a 0.36-year increase in Horvath DNAm-age. No PM2.5 species were selected by the LASSO in the Hannum DNAm-age models. Our findings persisted in sensitivity analyses including only visits with 1-year PM2.5 levels within US EPA national ambient air quality standards. CONCLUSION: Our results demonstrate that sulfate and ammonium were most associated with Horvath DNAm-age and suggest that DNAm-age measures differ in their sensitivity to ambient particle exposures and potentially disease. Published by Elsevier Ltd.
BACKGROUND: Long-term PM2.5 exposure and aging have been implicated in multiple shared diseases; studying their relationship is a promising strategy to further understand the adverse impact of PM2.5 on human health. OBJECTIVE: We assessed the relationship of major PM2.5 component species (ammonium, elemental carbon, organic carbon, nitrate, and sulfate) with Horvath and Hannum DNA methylation (DNAm) age, two DNA methylation-based predictors of chronological age. METHODS: This analysis included 552 participants from the Normative Aging Study with multiple visits between 2000 and 2011 (n=940 visits). We estimated 1-year PM2.5 species levels at participants' addresses using the GEOS-chem transport model. Blood DNAm-age was calculated using CpG sites on the Illumina HumanMethylation450 BeadChip. We fit linear mixed-effects models, controlling for PM2.5 mass and lifestyle/environmental factors as fixed effects, with the adaptive LASSO penalty to identify PM2.5 species associated with DNAm-age. RESULTS:Sulfate and ammonium were selected by the LASSO in the Horvath DNAm-age models. In a fully-adjusted multiple-species model, interquartile range increases in both 1-year sulfate (95%CI: 0.28, 0.74, P<0.0001) and ammonium (95%CI: 0.02, 0.70, P=0.04) levels were associated with at least a 0.36-year increase in Horvath DNAm-age. No PM2.5 species were selected by the LASSO in the Hannum DNAm-age models. Our findings persisted in sensitivity analyses including only visits with 1-year PM2.5 levels within US EPA national ambient air quality standards. CONCLUSION: Our results demonstrate that sulfate and ammonium were most associated with Horvath DNAm-age and suggest that DNAm-age measures differ in their sensitivity to ambient particle exposures and potentially disease. Published by Elsevier Ltd.
Entities:
Keywords:
DNA methylation age; Epigenetics; Long-term exposure; Particulate matter 2.5
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