大气细颗粒物显著降低人群的期望寿命，但对健康期望寿命的影响及机制均不明确。线虫是寿命研究的公认模式生物，已证实其部分基因与人类寿命调控基因同源。我们前期已采集完成了北京雾霾天气大气细颗粒物的成分分析，且预实验发现，细颗粒物对线虫寿命和健康寿命有不良影响。本课题拟采用线虫健康寿命研究技术，探明细颗粒物对健康寿命表型的毒性效应；再以RNA-Seq技术，筛选出细颗粒物影响线虫健康寿命表型的差异表达基因谱，采用GO及Pathway分析揭示其分子调控机制。同时，将线虫差异基因谱与GenAge库中人衰老/寿命基因进行同源性比对，筛检出细颗粒物影响人健康寿命的候选基因谱,为探查细颗粒物影响人群健康期望寿命的潜在生物标志物奠定实验基础，为今后细颗粒物人群健康风险的全面评估及干预提供科学依据。

The current literature reported that ambient fine particulate matter significantly reduce the Life Expectancy (LE）of human population, but the impact and its regulatory mechanism on healthspan in model organisms and human Health Adjusted Life Expectancy (HALE) are all unknown, which deserves further investigated. Nematode Caenorhabditis elegans (C.elegans) has been recognized as a powerful model organism on studying lifespan, for elucidating conserved pathways and processes relevant to human aging. Previously we have collected and analyzed the components of fine particulate matter from Beijing area, and pilot study found that fine particulate matter has adverse effects on lifespan and healthspan of C.elegans. This study designs to firstly detect the toxicity effect phenotype of fine particulate matter to healthspan of C. elegans by using the acknowledged C.elegans healthspan assay. Secondly, the fine particulate matter-induced differentially expressed genes relevant to the healthspan impact phenotype will be identified and verified by the RNA-Seq techniques, followed by the analysis of Gene Ontology（GO） and Pathway analysis, to explore the underlying molecular regulatory mechanism of ambient fine particulate matter on C. elegans healthspan. Moreover, the differential expressed genes/proteins in C. elegans will be compared the homology with those published human age-associated gene profile collected in the databank of GenAge (http://genomics.senescence.info/genes), further narrow down the candidate gene profiles related to human aging induced by ambient fine particulate matter. This study will provide the clue and critical evidence for future discovering the potential biomarkers of adverse impact of human HALE induced by ambient fine particulate matter, and future comprehensive popular health risk assessment of fine particulate matter and intervention strategies.

大气细颗粒物显著降低人群的期望寿命，但对健康期望寿命的影响及机制均不明确。线虫是寿命研究的公认模式生物，已证实其部分基因与人类寿命调控基因同源。我们采集完成了北京雾霾天气大气细颗粒物的成分分析，毒理学实验发现，水溶性细颗粒物对线虫寿命和健康寿命有不良影响。我们进一步采用RNA-Seq技术，筛选出细颗粒物影响线虫寿命表型的差异表达基因谱，采用GO及Pathway分析揭示其分子调控机制。同时，采用real-time PCR的方法，对部分基因的变化进行验证，为今后细颗粒物健康风险评估及干预提供实验科学依据。