Long-term ambient particle exposures and blood DNA methylation age: findings from the VA normative aging study

Nwanaji‐Enwerem, Jamaji C.; Colicino, Elena; Trevisi, Letizia; Kloog, Itai; Just, Allan C.; Shen, Jincheng; Brennan, Kasey; Dereix, Alexandra E.; Hou, Lifang; Vokonas, Pantel; Schwartz, Joel; Baccarelli, Andrea A.

doi:10.1093/eep/dvw006

Cited by 70 publications

(68 citation statements)

References 69 publications

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“…Horvath DNAm-age is a tissue-independent predictor of chronological age that is calculated from DNA methylation values at 353 chronological age-correlated CpG dinucleotides in Illumina’s HumanMethylation450 BeadChip (Horvath, 2013). Specifically, in an elderly cohort and with fully-adjusted models, we observed that a 1 μg/m 3 increase in 1-year PM 2.5 exposure was associated with a 0.52-year increase in Horvath DNAm-age (Nwanaji-Enwerem et al, 2016). …”

Section: Introductionmentioning

confidence: 84%

“…We then generated 1-year total PM 2.5 and PM 2.5 component species exposure windows by averaging daily exposures for the 365 days prior to the day of each participants’ NAS visit. The 1-year PM 2.5 exposure window was utilized because it has been previously reported to be robustly associated with DNAm-age (Nwanaji-Enwerem et al, 2016). …”

Section: Methodsmentioning

confidence: 99%

“…Specifically, our previous publication was the first study examining associations of ambient particles and DNAm-age (Nwanaji-Enwerem et al, 2016). There, we used a tiered approach of adding confounders and covariates based on known relationships of ambient particles with DNA methylation and known relationships of ambient particles with older markers of aging (Horvath, 2013; Madrigano et al, 2011; Baccarelli et al, 2009; Bind et al, 2015; Peng et al, 2016).…”

Section: Methodsmentioning

confidence: 99%

“…After considering model fit (assessed via AIC) and considering biological factors that are known to be important, the tier two covariates were deemed to be most appropriate. Thus, in line with the previously published tier two framework (Nwanaji-Enwerem et al, 2016), the models for this analysis were adjusted for chronological age (continuous), six blood cell type estimates [ i.e . plasma cells, CD4+ lymphocytes, CD8+ lymphocytes, natural killer (NK) cells, monocytes, and granulocytes] (continuous) determined via Houseman and Horvath methods (Horvath, 2013; Houseman et al, 2012), average 1-year temperature (continuous), cumulative cigarette pack years (continuous), smoking status (current, former, or never), season of visit (spring [March–May], Summer [June–August], Fall [September–November], and Winter [December–February]), body mass index (BMI) (lean [<25], overweight (Horvath and Ritz, 2015; Levine et al, 2015a, 2015b, 2015c; Horvath et al, 2014; Horvath, 2013), obese [>30]), alcohol intake (yes/no ≥2 drinks daily), and maximum years of education (continuous).…”

Section: Methodsmentioning

confidence: 99%

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Associations between long-term exposure to PM2.5 component species and blood DNA methylation age in the elderly: The VA normative aging study

Nwanaji‐Enwerem

Dai

Colicino

et al. 2017

Environment International

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Background Long-term PM2.5 exposure and aging have been implicated in multiple shared diseases; studying their relationship is a promising strategy to further understand the adverse impact of PM2.5 on human health. Objective We assessed the relationship of major PM2.5 component 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. Methods This analysis included 552 participants from the Normative Aging Study with multiple visits between 2000 and 2011 (n = 940 visits). We estimated 1-year PM2.5 species 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 PM2.5 mass and lifestyle/environmental factors as fixed effects, with the adaptive LASSO penalty to identify PM2.5 species associated with DNAm-age. Results 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 PM2.5 species were selected by the LASSO in the Hannum DNAm-age models. Our findings persisted in sensitivity analyses including only visits with 1-year PM2.5 levels within US EPA national ambient air quality standards. Conclusion 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.

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Section: Introductionmentioning

confidence: 84%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Associations between long-term exposure to PM2.5 component species and blood DNA methylation age in the elderly: The VA normative aging study

Nwanaji‐Enwerem

Dai

Colicino

et al. 2017

Environment International

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“…A previous study of epigenetic biomarkers of aging and air pollution using the NAS cohort observed positive associations between the epigenetic biomarkers and both PM 2.5 and BC [34]. Our analysis included additional epigenetic aging biomarkers (e.g.…”

Section: Discussionmentioning

confidence: 99%

Long-term exposure to air pollution is associated with biological aging

et al. 2016

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Long-term exposure to air pollution is associated with age-related diseases. We explored the association between accelerated biological aging and air pollution, a potential mechanism linking air pollution and health. We estimated long-term exposure to PM10, PM2.5, PM2.5 absorbance/black carbon (BC), and NOx via land-use regression models in individuals from the KORA F4 cohort. Accelerated biological aging was assessed using telomere length (TeloAA) and three epigenetic measures: DNA methylation age acceleration (DNAmAA), extrinsic epigenetic age acceleration (correlated with immune cell counts, EEAA), and intrinsic epigenetic age acceleration (independent of immune cell counts, IEAA). We also investigated sex-specific associations between air pollution and biological aging, given the published association between sex and aging measures. In KORA an interquartile range (0.97 μg/m3) increase in PM2.5 was associated with a 0.33 y increase in EEAA (CI = 0.01, 0.64; P = 0.04). BC and NOx (indicators or traffic exposure) were associated with DNAmAA and IEAA in women, while TeloAA was inversely associated with BC in men. We replicated this inverse BC-TeloAA association in the Normative Aging Study, a male cohort based in the USA. A multiple phenotype analysis in KORA F4 combining all aging measures showed that BC and PM10 were broadly associated with biological aging in men. Thus, we conclude that long-term exposure to air pollution is associated with biological aging measures, potentially in a sex-specific manner. However, many of the associations were relatively weak and further replication of overall and sex-specific associations is warranted.

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Association of Long-term Ambient Black Carbon Exposure and Oxidative Stress Allelic Variants With Intraocular Pressure in Older Men

et al. 2019

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IMPORTANCE Elevated intraocular pressure is a major risk factor for glaucoma, a leading cause of irreversible blindness worldwide. Environmental air pollution has been suggested as a potential contributor to elevated intraocular pressure; however, no studies have demonstrated such an association to date. OBJECTIVE To investigate the association of long-term ambient black carbon exposure with intraocular pressure in community-dwelling older adults. DESIGN, SETTING, AND PARTICIPANTS This population-based analysis, conducted from October 18, 2017, through March 22, 2018, used data from the all-male, New England-based Normative Aging Study of the US Department of Veterans Affairs. The analysis included 419 older men with a total of 911 follow-up study visits between January 1, 2000, and December 30, 2011. Intraocular pressure was measured by Goldmann applanation tonometry during the study visits. Validated spatiotemporal models were used to generate 1-year black carbon exposure levels at the addresses of the participants. MAIN OUTCOMES AND MEASURES An independently developed genetic score approach was used to calculate allelic risk scores for 3 pathways associated with black carbon toxicity: endothelial function, oxidative stress, and metal processing. The associations among black carbon exposure, allelic risk scores, and intraocular pressure were explored using linear mixed-effects models. RESULTS All 419 participants were men with a mean (SD) age of 75.3 (6.9) years. The mean (SD) 1-year black carbon exposure was 0.51 (0.18) μg/m 3 , and the mean (SD) intraocular pressure for the left eye was 14.1 (2.8) mm Hg and for the right eye was 14.1 (3.0) mm Hg. Of the 911 visits, 520 (57.1%) had a high endothelial function allelic risk score, 644 (70.7%) had a high metal-processing allelic risk score, and 623 (68.4%) had a high oxidative stress allelic risk score. In fully adjusted linear mixed-effects models, the association of black carbon with intraocular pressure was greater in individuals with a high oxidative stress allelic score (β = 0.36; 95% CI, 0.003-0.73) compared with individuals with a low score (β = −0.35; 95% CI, −0.86 to 0.15). CONCLUSIONS AND RELEVANCE Ambient black carbon exposure may be a risk factor for increased intraocular pressure in individuals susceptible to other biological oxidative stressors. If additional studies confirm these results, monitoring ambient black carbon exposure and physiological oxidative stress may prevent the development and progression of intraocular pressure-related disease.

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Long-term ambient particle exposures and blood DNA methylation age: findings from the VA normative aging study

Cited by 70 publications

References 69 publications

Associations between long-term exposure to PM2.5 component species and blood DNA methylation age in the elderly: The VA normative aging study

Associations between long-term exposure to PM2.5 component species and blood DNA methylation age in the elderly: The VA normative aging study

Long-term exposure to air pollution is associated with biological aging

Association of Long-term Ambient Black Carbon Exposure and Oxidative Stress Allelic Variants With Intraocular Pressure in Older Men

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