Impacts of the Mitochondrial Genome on the Relationship of Long-Term Ambient Fine Particle Exposure with Blood DNA Methylation Age

Jamaji C. Nwanaji-Enwerem*, Elena Colicino, Lingzhen Dai, Akin Cayir, Marco Sanchez-Guerra, Hannah E. Laue, Vy T. Nguyen, Qian Di, Allan C. Just, Lifang Hou, Pantel Vokonas, Brent A. Coull, Marc G. Weisskopf, Andrea A. Baccarelli, Joel D. Schwartz

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

The mitochondrial genome has long been implicated in age-related disease, but no studies have examined its role in the relationship of long-term fine particle (PM2.5) exposure and DNA methylation age (DNAm-age) - a novel measure of biological age. In this analysis based on 940 observations between 2000 and 2011 from 552 Normative Aging Study participants, we determined the roles of mitochondrial DNA haplogroup variation and mitochondrial genome abundance in the relationship of PM2.5 with DNAm-age. We used the GEOS-chem transport model to estimate address-specific, one-year PM2.5 levels for each participant. DNAm-age and mitochondrial DNA markers were measured from participant blood samples. Nine haplogroups (H, I, J, K, T, U, V, W, and X) were present in the population. In fully adjusted linear mixed-effects models, the association of PM2.5 with DNAm-age (in years) was significantly diminished in carriers of haplogroup V (Pinteraction = 0.01; β = 0.18, 95%CI: -0.41, 0.78) compared to noncarriers (β = 1.25, 95%CI: 0.58, 1.93). Mediation analysis estimated that decreases in mitochondrial DNA copy number, a measure of mitochondrial genome abundance, mediated 12% of the association of PM2.5 with DNAm-age. Our data suggests that the mitochondrial genome plays a role in DNAm-age relationships particularly in the context of long-term PM2.5 exposure.

Original languageEnglish (US)
Pages (from-to)8185-8195
Number of pages11
JournalEnvironmental Science and Technology
Volume51
Issue number14
DOIs
StatePublished - Jul 18 2017

ASJC Scopus subject areas

  • Chemistry(all)
  • Environmental Chemistry

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