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空气污染、颗粒物成分与基于甲基化的生物年龄。

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

机构信息

Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA.

Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA.

出版信息

Environ Int. 2019 Nov;132:105071. doi: 10.1016/j.envint.2019.105071. Epub 2019 Aug 3.

Abstract

BACKGROUND

Epigenetic age, as defined by DNA methylation, may be influenced by air pollution exposure.

OBJECTIVE

To evaluate the relationship between NO, 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, PM and NO using a model incorporating land-use regression and kriging. Predictive k-means was used to assign participants to clusters representing different PM 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, we stratified by cluster membership. We examined epigenome-wide associations using robust linear regression models corrected with false discovery rate q-values.

RESULTS

NO was inversely associated with age acceleration using the Hannum clock (β = -0.24, 95% CI: -0.47, -0.02). No associations were observed for PM. For PM, the association with age acceleration varied by PM component cluster. For example, with the Levine clock, an IQR increase in PM was associated with an over 6-year age acceleration in a cluster that has relatively high fractions of crustal elements relative to overall PM (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 was inversely associated with age acceleration (β = -1.33, 95% CI: -2.43, -0.23). Across the epigenome, NO 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 component profiles.

摘要

背景

DNA 甲基化定义的表观遗传年龄可能受到空气污染暴露的影响。

目的

评估 NO、颗粒物(PM)、PM 成分与加速表观遗传年龄之间的关系。

方法

在居住于美国大陆的非西班牙裔白人女性样本中(n=2747),我们使用结合土地利用回归和克里金的模型估计 PM、PM 和 NO 的住宅暴露情况。预测性 K 均值用于将参与者分配到代表不同 PM 成分特征的聚类中。我们使用 Illumina 的 Infinium HumanMethylation450 BeadChip 测量血液中的 DNA 甲基化(DNAm),并使用 Hannum、Horvath 和 Levine 表观遗传时钟计算 DNAm 年龄。根据 DNAm 年龄与实际年龄的回归残差定义年龄加速。我们使用线性回归估计污染物四分位距(IQR)增加与年龄加速之间的关联。对于 PM,我们按聚类成员身份进行分层。我们使用经过错误发现率 q 值校正的稳健线性回归模型进行全基因组关联分析。

结果

NO 与 Hannum 时钟的年龄加速呈负相关(β= -0.24,95%CI:-0.47,-0.02)。PM 与年龄加速无关。对于 PM,与年龄加速的关联因 PM 成分聚类而异。例如,使用 Levine 时钟,与 PM 相比,IQR 增加与具有相对较高地壳元素分数的聚类中超过 6 年的年龄加速相关(β= 6.57,95%CI:2.68,10.47),与具有相对较低硫分数的聚类中几乎 2 年的加速相关(β= 1.88,95%CI:0.51,3.25)。在一个以相对较低硝酸盐浓度为特征的聚类中,PM 与年龄加速呈负相关(β= -1.33,95%CI:-2.43,-0.23)。在整个表观基因组中,NO 与 2 个 CpG 位点的甲基化相关。

结论

在某些 PM 成分特征中,空气污染与表观遗传年龄相关,后者是死亡率和疾病风险的标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fcf/6754788/15a91793f0f0/nihms-1537078-f0001.jpg

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