William C Weston, Marie Abèle Bind, Wayne E Cascio, Robert B Devlin, David Diaz-Sanchez, Cavin K Ward-Caviness
{"title":"年轻、健康的成年人加速衰老和对臭氧暴露亚临床反应的改变。","authors":"William C Weston, Marie Abèle Bind, Wayne E Cascio, Robert B Devlin, David Diaz-Sanchez, Cavin K Ward-Caviness","doi":"10.1093/eep/dvae007","DOIUrl":null,"url":null,"abstract":"<p><p>Ozone exposure induces a myriad of adverse cardiopulmonary outcomes in humans. Although advanced age and chronic disease are factors that may exacerbate a person's negative response to ozone exposure, there are no molecular biomarkers of susceptibility. Here, we examine whether epigenetic age acceleration (EAA) is associated with responsiveness to short-term ozone exposure. Using data from a crossover-controlled exposure study (<i>n</i> = 17), we examined whether EAA, as measured in lung epithelial cells collected 24 h after clean air exposure, modifies the observed effect of ozone on autonomic function, cardiac electrophysiology, hemostasis, pulmonary function, and inflammation. EAA was assessed in lung epithelial cells extracted from bronchoalveolar lavage fluids, using the pan-tissue aging clock. We used two analytic approaches: (i) median regression to estimate the association between EAA and the estimated risk difference for subclinical responses to ozone and (ii) a block randomization approach to estimate EAA's effect modification of subclinical responses. For both approaches, we calculated Fisher-exact <i>P</i>-values, allowing us to bypass large sample size assumptions. In median regression analyses, accelerated epigenetic age modified associations between ozone and heart rate-corrected QT interval (QTc) ([Formula: see text]= 0.12, <i>P</i>-value = 0.007) and between ozone and C-reactive protein ([Formula: see text] = -0.18, <i>P</i> = 0.069). During block randomization, the directions of association remained consistent for QTc and C-reactive protein; however, the <i>P</i>-values weakened. Block randomization also revealed that responsiveness of plasminogen activator inhibitor-1 (PAI-1) to ozone exposure was modified by accelerated epigenetic aging (PAI-1 difference between accelerated aging-defined block groups = -0.54, <i>P</i>-value = 0.039). In conclusion, EAA is a potential biomarker for individuals with increased susceptibility to ozone exposure even among young, healthy adults.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"10 1","pages":"dvae007"},"PeriodicalIF":4.8000,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11155485/pdf/","citationCount":"0","resultStr":"{\"title\":\"Accelerated aging and altered subclinical response to ozone exposure in young, healthy adults.\",\"authors\":\"William C Weston, Marie Abèle Bind, Wayne E Cascio, Robert B Devlin, David Diaz-Sanchez, Cavin K Ward-Caviness\",\"doi\":\"10.1093/eep/dvae007\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Ozone exposure induces a myriad of adverse cardiopulmonary outcomes in humans. Although advanced age and chronic disease are factors that may exacerbate a person's negative response to ozone exposure, there are no molecular biomarkers of susceptibility. Here, we examine whether epigenetic age acceleration (EAA) is associated with responsiveness to short-term ozone exposure. Using data from a crossover-controlled exposure study (<i>n</i> = 17), we examined whether EAA, as measured in lung epithelial cells collected 24 h after clean air exposure, modifies the observed effect of ozone on autonomic function, cardiac electrophysiology, hemostasis, pulmonary function, and inflammation. EAA was assessed in lung epithelial cells extracted from bronchoalveolar lavage fluids, using the pan-tissue aging clock. We used two analytic approaches: (i) median regression to estimate the association between EAA and the estimated risk difference for subclinical responses to ozone and (ii) a block randomization approach to estimate EAA's effect modification of subclinical responses. For both approaches, we calculated Fisher-exact <i>P</i>-values, allowing us to bypass large sample size assumptions. In median regression analyses, accelerated epigenetic age modified associations between ozone and heart rate-corrected QT interval (QTc) ([Formula: see text]= 0.12, <i>P</i>-value = 0.007) and between ozone and C-reactive protein ([Formula: see text] = -0.18, <i>P</i> = 0.069). During block randomization, the directions of association remained consistent for QTc and C-reactive protein; however, the <i>P</i>-values weakened. Block randomization also revealed that responsiveness of plasminogen activator inhibitor-1 (PAI-1) to ozone exposure was modified by accelerated epigenetic aging (PAI-1 difference between accelerated aging-defined block groups = -0.54, <i>P</i>-value = 0.039). 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引用次数: 0
摘要
暴露于臭氧会对人体的心肺功能产生各种不良影响。虽然高龄和慢性疾病可能会加剧人对臭氧暴露的不良反应,但目前还没有易感性的分子生物标志物。在这里,我们研究了表观遗传年龄加速(EAA)是否与短期臭氧暴露的反应相关。利用一项交叉对照暴露研究(n = 17)的数据,我们研究了在清洁空气暴露 24 小时后收集的肺上皮细胞中测量的 EAA 是否会改变臭氧对自律神经功能、心脏电生理学、止血、肺功能和炎症的影响。我们使用泛组织老化时钟评估了从支气管肺泡灌洗液中提取的肺上皮细胞中的 EAA。我们采用了两种分析方法:(i) 中位回归法估算 EAA 与臭氧亚临床反应的估计风险差异之间的关联;(ii) 区块随机法估算 EAA 对亚临床反应的影响。对于这两种方法,我们都计算了费雪精确 P 值,从而绕过了大样本量假设。在中位回归分析中,加速表观遗传年龄改变了臭氧与心率校正 QT 间期(QTc)([计算公式:见正文]= 0.12,P 值 = 0.007)以及臭氧与 C 反应蛋白([计算公式:见正文]= -0.18,P = 0.069)之间的关联。在分块随机化过程中,QTc 和 C 反应蛋白的关联方向保持一致,但 P 值减弱。区组随机化还显示,纤溶酶原激活物抑制剂-1(PAI-1)对臭氧暴露的反应性受到加速表观遗传老化的影响(加速老化定义的区组之间的 PAI-1 差异 = -0.54,P 值 = 0.039)。总之,即使在年轻、健康的成年人中,EAA 也是一种潜在的生物标志物,可用于识别对臭氧暴露易感性增加的个体。
Accelerated aging and altered subclinical response to ozone exposure in young, healthy adults.
Ozone exposure induces a myriad of adverse cardiopulmonary outcomes in humans. Although advanced age and chronic disease are factors that may exacerbate a person's negative response to ozone exposure, there are no molecular biomarkers of susceptibility. Here, we examine whether epigenetic age acceleration (EAA) is associated with responsiveness to short-term ozone exposure. Using data from a crossover-controlled exposure study (n = 17), we examined whether EAA, as measured in lung epithelial cells collected 24 h after clean air exposure, modifies the observed effect of ozone on autonomic function, cardiac electrophysiology, hemostasis, pulmonary function, and inflammation. EAA was assessed in lung epithelial cells extracted from bronchoalveolar lavage fluids, using the pan-tissue aging clock. We used two analytic approaches: (i) median regression to estimate the association between EAA and the estimated risk difference for subclinical responses to ozone and (ii) a block randomization approach to estimate EAA's effect modification of subclinical responses. For both approaches, we calculated Fisher-exact P-values, allowing us to bypass large sample size assumptions. In median regression analyses, accelerated epigenetic age modified associations between ozone and heart rate-corrected QT interval (QTc) ([Formula: see text]= 0.12, P-value = 0.007) and between ozone and C-reactive protein ([Formula: see text] = -0.18, P = 0.069). During block randomization, the directions of association remained consistent for QTc and C-reactive protein; however, the P-values weakened. Block randomization also revealed that responsiveness of plasminogen activator inhibitor-1 (PAI-1) to ozone exposure was modified by accelerated epigenetic aging (PAI-1 difference between accelerated aging-defined block groups = -0.54, P-value = 0.039). In conclusion, EAA is a potential biomarker for individuals with increased susceptibility to ozone exposure even among young, healthy adults.