Life-course exposure to air pollution and biological ageing in the Lothian Birth Cohort 1936
Life-course exposure to air pollution and biological ageing in the Lothian Birth Cohort 1936
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DOI：
10.1101/2022.04.17.22273946
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发表时间：
2022-04
影响因子：
11.8
通讯作者：
Gergő Baranyi;I. Deary;D. McCartney;Sarah E. Harris;N. Shortt;Stefan Reis;Tom C. Russ;Catharine Ward
中科院分区：
文献类型：
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作者：
Gergő Baranyi;I. Deary;D. McCartney;Sarah E. Harris;N. Shortt;Stefan Reis;Tom C. Russ;Catharine Ward
背景：暴露于环境空气污染与一系列疾病有关。来自DNA甲基化（DNAm）的生物标志物表明了人类健康差异的潜在途径，将疾病发病机制和生物衰老联系起来。然而，人们对生命过程中的敏感时期知之甚少，在这些时期，空气污染可能对DNA m产生更大的影响，或者影响是否会随着时间的推移而积累。目的：我们研究了整个生命过程中空气污染暴露与基于DNA的衰老生物标志物之间的关联。方法：数据来自1936年洛锡安出生队列。参与者的居住历史与1935年、1950年、1970年、1980年、1990年和2001年左右的PM2.5、SO2、NO2和O3年度水平有关;污染物浓度使用EMEP 4UK大气化学传输模型进行估计。在70至80岁之间获得血液样品，并计算Horvath DNAmAge、Hannum DNAmAge、DNAmPhenoAge、DNAmGrimAge和DNAm端粒长度（DNAmTL）。我们应用了结构化生命过程建模方法：最小角度回归确定了空气污染综合指标（空气质量指数[AQI]）的最佳拟合生命过程模型，混合效应回归估计了AQI和单一污染物的选定模型。结果：我们纳入了525个个体，共1782个观察结果。在总样本中，1970年前后空气污染的增加与成年后期用Horvath DNAmAge测量的较高表观遗传年龄相关（AQI：B=0.622岁，95%CI：0.151，1.094）。我们发现，1980年左右空气污染较高的男性（AQI：B=-0.035千碱基，95%CI：-0.057，-0.014）和1935年左右空气污染较高的女性（AQI：B=-0.036千碱基，95%CI：-0.059，-0.013）的DNamTL较短。结果通过了DNAmTL的错误发现率校正，并且对于污染物PM2.5，SO2和NO2更一致。讨论：我们测试了空气污染和基于DNAm的生物标志物之间的生命过程关系。子宫内和成年中期的空气污染与后期生活中加速的表观遗传衰老和端粒相关衰老有关。
Background: Exposure to ambient air pollution is associated with a range of diseases. Biomarkers derived from DNA methylation (DNAm) indicate a potential pathway to human health differences, connecting disease pathogenesis and biological ageing. However, little is known about sensitive periods during the life course where air pollution might have a stronger impact on DNAm, or whether effects accumulate over time. Objectives: We examined associations between air pollution exposure across the life course and DNAm-based biomarkers of ageing. Methods: Data were derived from the Lothian Birth Cohort 1936. Participants residential history was linked to annual levels of PM2.5, SO2, NO2, and O3 around 1935, 1950, 1970, 1980, 1990, and 2001; pollutant concentrations were estimated using the EMEP4UK atmospheric chemistry transport model. Blood samples were obtained between ages of 70 and 80 years, and Horvath DNAmAge, Hannum DNAmAge, DNAmPhenoAge, DNAmGrimAge, and DNAm telomere length (DNAmTL) were computed. We applied the structured life-course modelling approach: least angle regression identified best-fit life-course models for a composite measure of air pollution (air quality index [AQI]), and mixed-effects regression estimated selected models for AQI and single pollutants. Results: We included 525 individuals with 1782 observations. In the total sample, increased air pollution around 1970 was associated with higher epigenetic age (AQI: b=0.622 year, 95%CI: 0.151, 1.094) measured with Horvath DNAmAge in late adulthood. We found shorter DNAmTL among males with higher air pollution around 1980 (AQI: b=-0.035 kilobase, 95%CI: -0.057, -0.014) and among females with higher exposure around 1935 (AQI: b=-0.036 kilobase, 95%CI: -0.059, -0.013). Findings passed false discovery rate correction for DNAmTL, and were more consistent for the pollutants PM2.5, SO2 and NO2. Discussion: We tested the life-course relationship between air pollution and DNAm-based biomarkers. Air pollution in utero and in young-to-mid adulthood is linked to accelerated epigenetic ageing and telomere-associated ageing in later life.