氯化有机磷酸酯诱导C.elegans衰老效应及健康风险机制

氯化有机磷酸酯在环境介质和生物体样本中广泛检出，对生态环境与人体健康构成严重威胁，其污染暴露能够诱导生物体产生多种退行性病变，但其诱导“衰老效应”的规律及健康风险机制尚未明确。本项目针对环境氯化有机磷酸酯暴露诱导生物体衰老效应规律及作用机制的科学问题，研究不同剂量暴露诱导C.elegans的毒性效应，阐明个体生理、生化特征影响和基因、蛋白表达差异，揭示急性、亚急性和慢性暴露诱导衰老效应的规律；采用转录组学、代谢组学、生物信息学、RNA干扰、转基因品系和突变体验证等学科交叉技术，识别诱导衰老显著相关的靶标基因、蛋白及生物标志物，阐明氧化自由基损伤和Insulin/IGF-1信号通路调控致衰过程的机理；采用体外细胞实验、同源建模和分子对接，阐明人体肝细胞衰老的同源基因、蛋白与信号通路，揭示人体组织赋存及脏器损害规律，为阐明氯化有机磷酸酯污染的环境与健康风险机制和构建预警、防控措施提供科学依据。

Chlorinated organophosphorus esters (ClOPEs) have been widely detected in various environmental media and biological sample worldwide, posing a serious threat to the environment and human health. ClOPEs exposure could induce multiple degenerative diseases, however the inducing of aging effect and molecular mechanisms of health risks remained largely unknown. This project selects Caenorhabditis elegans, the dominant model of aging research, as the test species to explore the aging-dependent toxicity effects induced by a typical ClOPEs. To detect the molecular regulation mechanisms related to aging such as oxidative free radical damage and the Insulin/insulin-like growth factor-1 signaling pathway, various methods including transcriptome sequencing and molecular docking would be used to deeply dig sensitive biomarkers, key target genes/proteins involved in the aging process. This study also establishes interactions between key target genes, proteins as well as their corresponding pathways and aging phenotypes. The results would clarify the molecular mechanisms of ClOPEs inducing the aging process and provide scientific supports for their pollution prevention and control measures.