Long-term Persistent Organic Pollutants Exposure Induced Telomere Dysfunction and Senescence-Associated Secretary Phenotype.
Long-term Persistent Organic Pollutants Exposure Induced Telomere Dysfunction and Senescence-Associated Secretary Phenotype.
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长期持久性有机污染物暴露引起端粒功能障碍和衰老相关的秘书表型
DOI：
10.1093/gerona/gly002
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发表时间：
2018-07-09
期刊：
影响因子：
--
通讯作者：
Wang F
中科院分区：
文献类型：
--
作者：
Yuan J;Liu Y;Wang J;Zhao Y;Li K;Jing Y;Zhang X;Liu Q;Geng X;Li G;Wang F
环境持久性有机污染物（POP）是指具有长距离大气传输、环境持久性和生物累积性的难降解有机化合物的统称。据报道，持久性有机污染物的累积可导致细胞DNA损伤以及对代谢健康产生不良影响。为了更好地理解持久性有机污染物相关健康风险的机制，我们于2009年至2016年在中国静海电子垃圾处理中心进行了一项基于证据的队列研究（n = 5955），该地区的人们遭受着严重的持久性有机污染物暴露。并且发现包括高血压、糖尿病、自身免疫性疾病和生殖障碍在内的多种与衰老相关的高水平疾病与持久性有机污染物暴露有关。在随后的分子水平研究中，观察到端粒功能障碍增加，包括端粒多重信号、无端粒信号末端、端粒缩短以及端粒替代延长激活，这可能是由DNA低甲基化修饰诱导的含端粒重复序列的RNA过度表达所致。此外，证实了由端粒功能障碍导致的衰老相关分泌表型，因为促炎细胞因子以及包括白细胞介素 - 6、P16INK4a和P14ARF在内的免疫衰老标志物受到了刺激。因此，我们提出端粒功能障碍和全身性慢性炎症升高导致了与衰老相关的疾病，这些疾病在持久性有机污染物暴露个体中高发。
Abstract Environmentally persistent organic pollutant (POP) is the general term for refractory organic compounds that show long-range atmospheric transport, environmental persistence, and bioaccumulation. It has been reported that the accumulation of POPs could lead to cellular DNA damage and adverse effects of on metabolic health. To better understand the mechanism of the health risks associated with POPs, we conducted an evidence-based cohort investigation (n = 5,955) at the Jinghai e-waste disposal center in China from 2009 to 2016, where people endure serious POP exposure. And high levels of aging-related diseases, including hypertension, diabetes, autoimmune diseases, and reproductive disorders were identified associated with the POP exposure. In the subsequent molecular level study, an increased telomere dysfunction including telomere multiple telomere signals, telomere signal-free ends, telomere shortening and activation of alternative lengthening of telomeres were observed, which might result from the hypomethylated DNA modification induced telomeric repeat-containing RNA overexpression. Moreover, dysfunctional telomere-leaded senescence-associated secretory phenotype was confirmed, as the proinflammatory cytokines and immunosenescence hallmarks including interleukin-6, P16INK4a, and P14ARF were stimulated. Thus, we proposed that the dysfunctional telomere and elevated systemic chronic inflammation contribute to the aging-associated diseases, which were highly developed among the POP exposure individuals.
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影响因子：
14.9
作者：
Cawthon RM
通讯作者：
Cawthon RM
DOI：
10.1073/pnas.0604602103
发表时间：
2006-09-19
影响因子：
11.1
作者：
Egger, Gerda;Jeong, Shinwu;Liang, Gangning
通讯作者：
Liang, Gangning
影响因子：
16.6
作者：
Jurk, Diana;Wilson, Caroline;Passos, Joao F.;Oakley, Fiona;Correia-Melo, Clara;Greaves, Laura;Saretzki, Gabriele;Fox, Chris;Lawless, Conor;Anderson, Rhys;Hewitt, Graeme;Pender, Sylvia L. F.;Fullard, Nicola;Nelson, Glyn;Mann, Jelena;van de Sluis, Bart;Mann, Derek A.;von Zglinicki, Thomas
通讯作者：
von Zglinicki, Thomas
暴露于环境内分泌破坏者和儿童发育。
DOI：
10.1001/archpediatrics.2012.241
发表时间：
2012-06-01
影响因子：
--
作者：
Meeker, John D.
通讯作者：
Meeker, John D.
影响因子：
64.8
作者：
Flynn, Rachel Litman;Centore, Richard C.;O'Sullivan, Roderick J.;Rai, Rekha;Tse, Alice;Zhou Songyang;Chang, Sandy;Karlseder, Jan;Zou, Lee
通讯作者：
Zou, Lee