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Published January 1, 2017 | Version v1
Journal article Open

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

Creators

  • 1. Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA
  • 2. Columbia Mailman Sch Publ Hlth, Dept Environm Hlth Sci, New York, NY 10032 USA
  • 3. Icahn Sch Med Mt Sinai, Dept Environm Med & Publ Hlth, New York, NY 10029 USA
  • 4. Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Ctr Populat Epigenet,Dept Prevent Med, Chicago, IL 60611 USA
  • 5. Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA

Description

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 (P-interaction = 0.01; beta = 0.18, 95%CI: -0.41, 0.78) compared to noncarriers (beta = 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.

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