title: Associations between long-term exposure to PM2.5component species and blood DNA methylation age in the elderly: The VA normative aging study.
abstract: Long-term PM2.5exposure and aging have been implicated in multiple shared diseases; studying their relationship is a promising strategy to further understand the adverse impact of PM2.5on human health.
  
  
  
  We assessed the relationship of major PM2.5component 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.
  
  
  
  This analysis included 552 participants from the Normative Aging Study with multiple visits between 2000 and 2011 (n=940 visits). We estimated 1-year PM2.5species 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 PM2.5mass and lifestyle/environmental factors as fixed effects, with the adaptive LASSO penalty to identify PM2.5species associated with DNAm-age.
  
  
  
  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 PM2.5species were selected by the LASSO in the Hannum DNAm-age models. Our findings persisted in sensitivity analyses including only visits with 1-year PM2.5levels within US EPA national ambient air quality standards.
  
  
  
  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.
authors.affiliation: Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA. Electronic address: jnwanajienwerem@g.harvard.edu.
authors.forename: Jamaji C
authors.initials: JC
authors.lastname: Nwanaji-Enwerem
authors.affiliation: Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Lingzhen
authors.initials: L
authors.lastname: Dai
authors.affiliation: Department of Environmental Health Sciences, Columbia Mailman School of Public Health, New York, NY, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Colicino
authors.affiliation: Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Youssef
authors.initials: Y
authors.lastname: Oulhote
authors.affiliation: Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Di
authors.affiliation: Department of Geography and Environmental Development, Ben-Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Itai
authors.initials: I
authors.lastname: Kloog
authors.affiliation: Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Allan C
authors.initials: AC
authors.lastname: Just
authors.affiliation: Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Lifang
authors.initials: L
authors.lastname: Hou
authors.affiliation: VA Normative Aging Study, Veterans Affairs Boston Healthcare System, The Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Pantel
authors.initials: P
authors.lastname: Vokonas
authors.affiliation: Department of Environmental Health Sciences, Columbia Mailman School of Public Health, New York, NY, USA.
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Baccarelli
authors.affiliation: Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Marc G
authors.initials: MG
authors.lastname: Weisskopf
authors.affiliation: Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Joel D
authors.initials: JD
authors.lastname: Schwartz
mesh_terms: D000368:Aged; D000375:Aging / Q000097:blood* / Q000235:genetics; D000393:Air Pollutants / Q000032:analysis* / Q000633:toxicity; D004247:DNA / Q000097:blood*; D019175:DNA Methylation / Q000187:drug effects*; D004784:Environmental Monitoring / Q000379:methods*; D005260:Female; D006801:Humans; D019570:Inhalation Exposure / Q000032:analysis; D008297:Male; D010316:Particle Size; D052638:Particulate Matter / Q000032:analysis* / Q000633:toxicity; D014481:United States; D014484:United States Environmental Protection Agency
chemical_list: D000393:Air Pollutants; D052638:Particulate Matter; D004247:DNA
keywords: DNA methylation age; Epigenetics; Long-term exposure; Particulate matter 2.5