title: Long-term ambient particle exposures and blood DNA methylation age: findings from the VA normative aging study.
abstract: BACKGROUND
  Ambient particles have been shown to exacerbate measures of biological aging; yet, no studies have examined their relationships with DNA methylation age (DNAm-age), an epigenome-wide DNA methylation based predictor of chronological age.
  
  
  OBJECTIVE
  We examined the relationship of DNAm-age with fine particulate matter (PM2.5), a measure of total inhalable particle mass, and black carbon (BC), a measure of particles from vehicular traffic.
  
  
  METHODS
  We used validated spatiotemporal models to generate 1-year PM2.5and BC exposure levels at the addresses of 589 older men participating in the VA Normative Aging Study with 1-3 visits between 2000 and 2011 (n= 1032 observations). Blood DNAm-age was calculated using 353 CpG sites from the Illumina HumanMethylation450 BeadChip. We estimated associations of PM2.5and BC with DNAm-age using linear mixed effects models adjusted for age, lifestyle/environmental factors, and aging-related diseases.
  
  
  RESULTS
  After adjusting for covariates, a 1-µg/m3increase in PM2.5(95% CI: 0.30, 0.75,P<0.0001) was significantly associated with a 0.52-year increase in DNAm-age. Adjusted BC models showed similar patterns of association (β = 3.02, 95% CI: 0.48, 5.57,P= 0.02). Only PM2.5(β = 0.54, 95% CI: 0.24, 0.84,P= 0.0004) remained significantly associated with DNAm-age in two-particle models. Methylation levels from 20 of the 353 CpGs contributing to DNAm-age were significantly associated with PM2.5levels in our two-particle models. Several of these CpGs mapped to genes implicated in lung pathologies includingLZTFL1, PDLIM5, andATPAF1.
  
  
  CONCLUSIONS
  Our results support an association of long-termambient particle levels with DNAm-age and suggest that DNAm-age is a biomarker of particle-related physiological processes.
authors.affiliation: Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
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: 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: Letizia
authors.initials: L
authors.lastname: Trevisi
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 Preventive Medicine, 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 Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Jincheng
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Kasey
authors.initials: K
authors.lastname: Brennan
authors.affiliation: Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Dereix
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 and 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, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Schwartz
authors.affiliation: Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Baccarelli
keywords: DNA methylation age; Epigenetics; black carbon; particulate matter 2.5