Air pollution, particulate matter composition and methylation-based biologic age

Abstract

Background: Epigenetic age, as defined by DNA methylation, may be influenced by air pollution exposure. Objective: To evaluate the relationship between NO 2 , particulate matter (PM), PM components and accelerated epigenetic age. Methods: In a sample of non-Hispanic white women living in the contiguous U.S. (n = 2747), we estimated residential exposure to PM 2.5 , PM 10 and NO 2 using a model incorporating land-use regression and kriging. Predictive k -means was used to assign participants to clusters representing different PM 2.5 component profiles. We measured DNA methylation (DNAm) in blood using the Illumina's Infinium HumanMethylation450 BeadChip and calculated DNAm age using the Hannum, Horvath and Levine epigenetic clocks. Age acceleration was defined based on residuals after regressing DNAm age on chronological age. We estimated associations between interquartile range (IQR) increases in pollutants and age acceleration using linear regression. For PM 2.5 , we stratified by cluster membership. We examined epigenome-wide associations using robust linear regression models corrected with false discovery rate q-values. Results: NO 2 was inversely associated with age acceleration using the Hannum clock (β = −0.24, 95% Cl: − 0.47, −0.02). No associations were observed for PM 10 . For PM 2.5 , the association with age acceleration varied by PM 2.5 component cluster. For example, with the Levine clock, an IQR increase in PM 2.5 was associated with an over 6-year age acceleration in a cluster that has relatively high fractions of crustal elements relative to overall PM 2.5 (β = 6.57, 95% CI: 2.68, 10.47), and an almost 2-year acceleration in a cluster characterized by relatively low sulfur fractions (β = 1.88, 95% CI: 0.51, 3.25). In a cluster distinguished by lower relative nitrate concentrations, PM 2.5 was inversely associated with age acceleration (β = −1.33, 95% CI: −2.43, −0.23). Across the epigenome, NO 2 was associated with methylation at 2 CpG sites. Conclusion: Air pollution was associated with epigenetic age, a marker of mortality and disease risk, among certain PM 2.5 component profiles.

Epigenetic mortality predictors and incidence of breast cancer

“…For example, epigenetic clocks were designed to capture age effects and are associated with breast cancer incidence [25]. Single CpGs are also associated with breast cancer incidence [39,40] and may be sensitive to emerging and established breast cancer risk factors [41][42][43][44][45][46]. Future efforts to design epigenetic breast cancer predictors may therefore be aided by selecting CpGs associated with both breast cancer risk factors as well as the disease itself.…”

DNA Methylation in the Adipose Tissue and Whole Blood of Agent Orange-exposed Operation Ranch Hand Veterans

“…For each clock, only chronological age was signi cantly correlated with methylation age (Hannum clock: r=0.900 p<0.01; Horvath clock: r=0.882, p<0.01; PhenoAge clock: r=0.880, p<0.01). Age acceleration was calculated by regressing methylation age on chronological age and taking the residuals of the model [44]. We constructed linear models with age acceleration as the outcome and dioxin level as the predictor (see methods).…”

“…We completed the Hannum and Horvath clock analyses through the wateRmelon package; the PhenoAge clock was accessed through the ENmix package. For each participant, we calculated age acceleration by regressing methylation age on chronological age and taking the residuals from the model [44]. We examined possible associations between age acceleration and dioxin burden using linear models.…”

The Challenge by Multiple Environmental and Biological Factors Induce Inflammation in Aging: Their Role in the Promotion of Chronic Disease

“…There is evidence of the existence of methylation, acetylation and phosphorylation of histones H3 and H4, markers found in genes involved in the activation of immune cells and cardiovascular diseases ( 200 , 202 – 205 ). Altogether, air pollutants can generate DNA adducts promoting carcinogenesis and deteriorate telomerase activity, as reviewed by Martens and Nawrot (2016), and contributing to continuous DNA damage and premature aging ( 206 , 207 ).…”

“…The resolution appears to depend on the exposure context. Acute exposure would result in high levels of ROS and damage, whereas prolonged stimulation, even a low-grade one, generates a constant production of ROS and chronic low-grade inflammation ( 187 ), consequent with the potentiation of disease risk and an epigenetic age acceleration ( 206 ), promoting pathological aging.…”