Associations between long-term exposure to PM2.5 components and epigenetic age acceleration Restricted; Files Only

Abstract

Objective

Epigenetic age acceleration (EAA) quantifies the difference between biological and chronological age and is linked to age-related diseases. While fine particulate matter (PM2.5) has been associated with EAA, the impact of particular components remains unclear. We examined associations between long-term exposure to major PM2.5 component mixtures and EAA in cognitively healthy adults from the Emory Healthy Brains Study (EHBS).

 

Material and Methods

We analyzed 620 adults (45-76 years) from the EHBS in Georgia, USA (2016-2018). Residential exposure to elemental carbon (EC), organic carbon (OC), ammonium (NH4⁺), nitrate (NO3^-), and sulfate (SO4^2-) was estimated at a 50m-1km resolution and averaged over 3-, 5-, 10-, and 15-year periods before blood collection. We measured whole blood DNA methylation using the Infinium MethylationEPIC v1.0 array and calculated EAA using four epigenetic clocks (Horvath, Horvath Skin and Blood, Hannum, GrimAge) and pace-of-aging using the DunedinPACE clock. Single-pollutant linear regression models estimated associations between PM2.5 components and EAA and pace-of-aging, adjusting for demographics and neighborhood deprivation. Novel environmental mixture methods—Bayesian Weighted Sums (BWS), Weighted Quantile Sums (WQS), and quantile g-computation (QGcomp)—assessed overall mixture effects and individual component contributions.

 

Results

NH4⁺ and SO4^2- were associated with increased GrimAge (e.g., per 0.07 µg/m³ IQR increase in NH4⁺: 3-year: 0.20 year [0.09, 0.31]; 15-year: 0.14 [0.05, 0.22]) and Hannum EAA (e.g., 3-year: 0.26 year [0.10, 0.43]; 15-year: 0.14 year [0.02, 0.27]). BWS, WQS, and QGcomp identified significant overall mixture effects for the PM2.5 components with GrimAge and Hannum EAA, with NH4⁺ and SO4^2- contributing the most to the overall effect (e.g., 3-year: NH4⁺ and SO4^2- explained 59.3% of the GrimAge EAA effect). Pace-of-aging results contradicted our hypothesis, with increased NH4⁺ levels being associated with decreased pace-of-aging (e.g., 3-year: -0.005 year [-0.009, -0.001]; 5-year: -0.005 [-0.009, -0.0003]; 10-year: -0.004 [-0.007, -0.001]). BWS and QGcomp also identified significant negative overall mixture effects for the PM2.5 components and pace-of-aging.

 

Conclusion

PM2.5 component mixtures were associated with EAA, particularly for shorter exposures and increased NH4⁺ and SO4^2- levels. Reducing exposure to these pollutants may help mitigate long-term health impacts for aging-related diseases. The inverse associations between NH4⁺ and pace-of-aging were unexpected and warrant further investigation.

Table of Contents

Background Methods Study Population Exposure Assessment DNA Methylation and Epigenetic Clocks Covariates Statistical Methods Effect Modification Analyses Sensitivity Analyses Results Study Population PM2.5 Components and EAA Effect Modification Analyses PM2.5 Components and Pace-of-Aging Sensitivity Analyses Discussion

About this Master's Thesis

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School	Rollins School of Public Health
Department	Epidemiology
Subfield / Discipline	Epidemiology - MPH & MSPH
Degree	M.S.P.H.
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Epidemiology
Palabra Clave	Mixtures analysis Epigenomics Particle components Long-term exposure Air pollution
Committee Chair / Thesis Advisor	Anke Huels, Emory University

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