一生中接触的空气污染与洛锡安出生队列 1936 年研究中的生物老化。
Life-course exposure to air pollution and biological ageing in the Lothian Birth Cohort 1936.
机构信息
Centre for Research on Environment, Society and Health, School of GeoSciences, The University of Edinburgh, Edinburgh, UK.
Lothian Birth Cohorts, Department of Psychology, The University of Edinburgh, Edinburgh, UK.
出版信息
Environ Int. 2022 Nov;169:107501. doi: 10.1016/j.envint.2022.107501. Epub 2022 Sep 6.
BACKGROUND
Exposure to air pollution is associated with a range of diseases. Biomarkers derived from DNA methylation (DNAm) offer potential mechanistic insights into 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. We examined associations between air pollution exposure across the life course and DNAm-based markers of biological ageing.
METHODS
Data were derived from the Scotland-based Lothian Birth Cohort 1936. Participants' residential history was linked to annual levels of fine particle (PM), sulphur dioxide (SO), nitrogen dioxide (NO), and ozone (O) 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 = 0.322 year, 95 %CI: 0.088, 0.555) measured with Horvath DNAmAge in late adulthood. We found shorter DNAmTL among males with higher air pollution around 1980 (AQI: b = -0.015 kilobase, 95 %CI: -0.027, -0.004) and among females with higher exposure around 1935 (AQI: b = -0.017 kilobase, 95 %CI: -0.028, -0.006). Findings were more consistent for the pollutants PM, SO and NO.
DISCUSSION
We tested the life-course relationship between air pollution and DNAm-based biomarkers. Air pollution around birth and in young-to-middle adulthood is linked to accelerated epigenetic ageing and telomere-associated ageing in later life.
背景
暴露于空气污染与一系列疾病有关。源自 DNA 甲基化（DNAm）的生物标志物为人类健康差异提供了潜在的机制见解，将疾病发病机制与生物衰老联系起来。然而，人们对于在生命过程中空气污染可能具有更强影响的敏感时期，或者随着时间的推移，影响是否会累积，知之甚少。我们研究了整个生命过程中空气污染暴露与基于 DNAm 的生物衰老标志物之间的关联。
方法
数据来自苏格兰的洛锡安出生队列 1936 年。参与者的居住史与 1935 年、1950 年、1970 年、1980 年、1990 年和 2001 年的细颗粒物（PM）、二氧化硫（SO）、二氧化氮（NO）和臭氧（O）的年度水平相关联；使用 EMEP4UK 大气化学输送模型估算污染物浓度。血液样本在 70 至 80 岁之间采集，并计算出霍瓦特 DNAmAge、汉纳姆 DNAmAge、DNAmPhenoAge、DNAmGrimAge 和 DNAm 端粒长度（DNAmTL）。我们应用结构生命历程建模方法：最小角度回归确定了空气污染综合指标（空气质量指数 [AQI]）的最佳拟合生命历程模型，混合效应回归估计了 AQI 和单个污染物的选定模型。
结果
我们纳入了 525 名参与者，共有 1782 次观察。在总样本中，成年后期，1970 年左右空气污染增加与表观年龄更高有关（AQI：b=0.322 岁，95%CI：0.088，0.555）。我们发现，1980 年左右男性的空气污染较高，与 DNAmTL 较短有关（AQI：b=-0.015 千碱基，95%CI：-0.027，-0.004），1935 年左右女性的空气污染较高，与 DNAmTL 较短有关（AQI：b=-0.017 千碱基，95%CI：-0.028，-0.006）。对于 PM、SO 和 NO 等污染物，结果更为一致。
讨论
我们测试了空气污染与基于 DNAm 的生物标志物之间的生命历程关系。出生前后和年轻到中年的空气污染与晚年加速的表观遗传衰老和端粒相关衰老有关。
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