大肠杆菌基因变异株对秀丽隐杆线虫衰老与寿命的影响及其机理研究

Gut microbes influence host physiology such as development, reproduction, metabolism and immunity. They play a significant role in the health and aging of the host animals, and thus provide a potential target for efforts that slow aging and extend longevity.However, the mechanisms by which gut microbes influence the host longevityremain unrevealed. This project aims to use Caenorhabditis elegans as host animal and systematically investigate the influence of Escherichia coli single-gene knockout mutants on the worm’s longevity. Furthermore, the mechanisms by which the E. coli mutants influence the aging process of C. elegans will be explored. The physiological properties of the mutants will be predicted based on information about the function of the mutated genes. Mutants that can influence the host longevity will be screened and potential key products that cause such influence will be analyzed by methods such as LC-MS. And then, C. elegans mutants will be used to test the aging-involved signal pathways by which the E. coli mutants or their metabolites likely take effect. The results will improve our understandings of the mechanisms by which the gut microbes influence the aging and longevity of their host, and provide theories for further efforts to slow aging and extend longevity by regulating gut microbiota.

肠道菌影响宿主的发育、繁殖、代谢和免疫等生理功能，对宿主生物的健康和衰老起着至关重要的作用，是延缓宿主衰老、延长寿命的潜在调控目标。然而到目前为止，肠道菌影响宿主衰老和寿命的分子机制还有待阐明。本项目计划以秀丽隐杆线虫为宿主生物，系统研究大肠杆菌单基因敲除库中的变异株对线虫寿命的影响，并进一步探索基因变异株影响宿主寿命的作用机理。项目将通过生物信息学方法预测各基因突变对大肠杆菌生理生化特性的影响，目的性地筛选能够影响线虫衰老进程与寿命的变异株，并利用液质联用等方法检测变异株中可能起关键作用的代谢物或细胞组分。此后，将利用线虫相关基因突变体进行寿命试验以检验大肠杆菌变异株影响线虫衰老可能涉及的信号通路，从而揭示作用机理。本项目的结果将推进肠道菌对宿主生物衰老与寿命的作用机制方面理论的发展，为通过调控宿主肠道菌群以延缓衰老、延长寿命的研究奠定基础。

肠道菌对多细胞宿主生物体的各种生理功能起着至关重要的作用，是促进宿主健康长寿的潜在调控目标，其作用方式的研究具有重要的科学意义。本项目研究了大肠杆菌单基因缺陷株对秀丽隐杆线虫衰老和发育过程的影响，并对其中涉及的细菌代谢产物及其可能的作用机理进行了探索。实验观察到大肠杆菌tgt基因缺陷株对线虫寿命有一定延长作用，该基因与大肠杆菌代谢产物Q物质的合成有关。通过检测daf-2及daf-16基因突变线虫中脂褐素积累量的变化发现，与野生型大肠杆菌饲喂的线虫相比，基因缺陷株饲喂的线虫并无显著差异，可以推测tgt基因缺陷菌株对于线虫衰老的影响可能与IIS通路有关。进一步研究了Q合成相关菌株对线虫发育造成的影响，发现与野生型菌株饲喂的线虫相比，以yadB、ybaX、ygcM缺陷菌株为食的线虫发育期的体长缩短，而基因回补或Q物质的添加使该效果消失。由于在绝大部分真核生物中没有Q的合成途径，都需要从细菌中获取，因而该物质属于微量营养素的一种。本项目中关于该物质合成基因缺陷株影响宿主衰老和发育的发现，对于未来进一步研究其对更高等动物的作用具有良好的启示意义。