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

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 non-carriers (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.

Prenatal particulate matter exposure and mitochondrial dysfunction at the maternal-fetal interface: Effect modification by maternal lifetime trauma and child sex

“…For instance, in a cross-sectional study of occupational workers, exposure to particulate matter (PM 10 and PM 1 ) and low-dose benzene was associated with higher mtDNAcn in blood (Hou et al, 2010; Carugno et al, 2012); however, in a repeated measure analysis of exposure to PM or elemental carbon, researchers observed increases in exposure to be associated with lower mtDNAcn (Hou et al, 2013). Similarly, long-term PM 2.5 exposure was associated with decreased mtDNAcn in the Normative Aging Study (Nwanaji-Enwerem et al, 2017). Only two studies have investigated the impact of prenatal exposure to PM on mtDNAcn in cord blood (Janssen et al, 2012; Rosa et al, 2017a); one of these studies also reported results in placenta (Janssen et al, 2012).…”

Relationships of Long-Term Smoking and Moist Snuff Consumption With a DNA Methylation Age Relevant Smoking Index: An Analysis in Buccal Cells

“…18,[27][28][29] Moreover, DNAm-age has been linked to molecular process involving metabolism, the immune system, cellular aging, and cancer. [30][31][32][33][34][35] We hypothesized that this molecularly informative 66-CpG SI could also be applied to buccal cells. Buccal cells are of particular interest for tobacco smoke exposure, because they are among the few cell types directly exposed to tobacco smoke.…”

Polyamine Metabolism and Gene Methylation in Conjunction with One-Carbon Metabolism

“…Various types of cellular stress seem to affect epigenetic alterations that may lead to deleterious consequences. Exposure to fine particle air pollution affects DNA methylation status in blood cells [ 178 , 179 , 180 , 181 , 182 , 183 ] and placenta [ 184 ]. Cigarette smoking has adverse effects on health and is associated with changes in epigenetic marks.…”