• 通过筛选3983个大肠杆菌突变体,发现删除其中29个基因,促进秀丽隐杆线虫的寿命,而许多突变体还阻止肿瘤生长和淀粉样β蛋白积累;
  • 突变体通过多糖可拉酸(CA)来调节线粒体动力学和未折叠蛋白响应(UPRmt),这促进长寿;
  • 纯化的CA聚合物则通过响应UPRmt的转录因子ATFS-1以显著促进宿主的寿命,这样的效果在不同物种中均呈现;
  • 这是首次发现促长寿微生物的分子靶点以及相关细菌代谢产物。
蓝灿辉 | 热心肠先生
Cell [IF:38.637]

Microbial Genetic Composition Tunes Host Longevity



2017-06-15, Article

Abstract & Authors:展开

Highlights: Systematic analysis of longevity-promoting microbial genetic variations Colanic acid as a pro-longevity natural compound effective in different species Bacterial metabolites regulate host mitochondrial dynamics and UPR
SUMMARY: Homeostasis of the gut microbiota critically influences host health and aging. Developing genetically engineered probiotics holds great promise as a new therapeutic paradigm to promote healthy aging. Here, through screening 3,983 Escherichia coli mutants, we discovered that 29 bacterial genes, when deleted, increase longevity in the host Caenorhabditis elegans. A dozen of these bacterial mutants also protect the host from age-related progression of tumor growth and amyloid-beta accumulation. Mechanistically, we discovered that five bacterial mutants promote longevity through increased secretion of the polysaccharide colanic acid (CA), which regulates mitochondrial dynamics and unfolded protein response (UPRmt) in the host. Purified CA polymers are sufficient to promote longevity via ATFS-1, the host UPRmt-responsive transcription factor. Furthermore, the mitochondrial changes and longevity effects induced by CA are conserved across different species. Together, our results identified molecular targets for developing pro-longevity microbes and a bacterial metabolite acting on host mitochondria to promote longevity.

First Authors:
Bing Han

Correspondence Authors:
Meng C Wang

All Authors:
Bing Han,Priya Sivaramakrishnan,Chih-Chun J Lin,Isaiah A A Neve,Jingquan He,Li Wei Rachel Tay,Jessica N Sowa,Antons Sizovs,Guangwei Du,Jin Wang,Christophe Herman,Meng C Wang