GCS-Groupement des Hôpitaux de l'Institut Catholique de Lille, Gerontology Clinic, Faculté Libre de Médecine, Lille 59000, France; Unité de Chimie Environnementale et Interactions sur le Vivant (EA4492), Université du Littoral Côte d'Opale, Dunkerque 59140, France.
Unité de Chimie Environnementale et Interactions sur le Vivant (EA4492), Université du Littoral Côte d'Opale, Dunkerque 59140, France.
Exp Gerontol. 2018 Sep;110:125-132. doi: 10.1016/j.exger.2018.05.018. Epub 2018 May 31.
Classified as carcinogenic to humans by the IARC in 2013, fine air particulate matter (PM) can be inhaled and retained into the lung or reach the systemic circulation. This can cause or exacerbate numerous pathologies to which the elderly are often more sensitive.
In order to estimate the influence of age on the development of early cellular epigenetic alterations involved in carcinogenesis, peripheral blood mononuclear cells sampled from 90 patients from three age classes (25-30, 50-55 and 75-80 years old) were ex vivo exposed to urban PM.
Particles exposure led to variations in telomerase activity and telomeres length in all age groups without any influence of age. Conversely, P16 gene expression increased significantly with age after exposure to PM. Age could enhance MGMT gene expression after exposure to particles, by decreasing the level of promoter methylation in the oldest people.
Hence, our results demonstrated several tendencies in cells modification depending on age, even if all epigenetic assays were carried out after a limited exposure time allowing only one or two cell cycles. Since lung cancer symptoms appear only at an advanced stage, our results underline the needs for further investigation on the studied biomarkers for early diagnosis of carcinogenesis to improve survival.
2013 年国际癌症研究机构（IARC）将细颗粒物（PM）归类为人类致癌物质，可吸入并滞留在肺部或进入全身循环。这可能导致或加剧老年人更容易出现的许多病理变化。
为了评估年龄对致癌发生过程中早期细胞表观遗传改变的影响，从三个年龄组（25-30 岁、50-55 岁和 75-80 岁）的 90 名患者中抽取外周血单核细胞，在体外暴露于城市 PM 下。
颗粒暴露导致所有年龄组的端粒酶活性和端粒长度发生变化，而年龄没有影响。相反，暴露于 PM 后，P16 基因表达随着年龄的增长而显著增加。暴露于颗粒后，MGMT 基因的表达在年龄较大的人群中增强，这是由于启动子甲基化水平降低。
因此，我们的结果表明，即使所有的表观遗传检测都是在有限的暴露时间内进行的，只允许一个或两个细胞周期，细胞的修饰也会根据年龄出现几种趋势。由于肺癌症状仅在晚期出现，因此我们的结果强调需要进一步研究所研究的生物标志物，以进行早期诊断致癌发生，提高生存率。
