Discovery of chemical compounds with high aging-delaying, health-improving and lifespan-extending efficiencies and characterization of their action mechanisms

利用NSERC Engage and Engage Plus赠款提供的资金，我们筛选了一个植物提取物(PE)文库，以寻找可以延缓酿酒酵母时间老化的提取物。资料库由蒙特利尔地区的一家公司Idunn Technologies Inc.提供。我们的初步筛选显示，6种PE能显著延长酵母的实际寿命，比任何已知的延长寿命的化合物都要大得多。我们证明了最初发现的6种PE中的每一种都是一种GeroProtector，可以引起荷尔蒙应激反应，影响一组独特的定义长寿的细胞过程，并通过不同的信号通路和融合到进化保守网络中的蛋白激酶来减缓酵母的时间衰老。我们最近对Idunn Technologies Inc.提供的PES库进行了筛选，发现了另外15种可延缓酵母时间老化的提取物。根据目前的研究建议，我们申请为期3年的CRD补助金。拟议的CRD项目将：1)确定我们发现的21个PE中每一个都对延缓衰老负责的化合物；2)评估最近发现的15个延缓衰老的PE如何影响一组独特的定义长寿的细胞过程；3)调查最近发现的15个延缓衰老的植物提取物如何影响定义长寿的信号通路和蛋白激酶网络；以及4)检查21个PE的一些组合是否对彼此的延缓衰老效率具有相加或协同作用。这里提出的研究项目将：1)促进当前对生物衰老复杂性背后的机制的理解；2)刺激两名研究生的专业发展；3)使Idunn Technologies Inc.能够开发出具有最大延缓衰老和延长寿命效果的天然保健品的新配方；4)使Idunn Technologies Inc.能够获得我们康科迪亚大学实验室提供的独特知识、专业知识和演绎资源；以及5)对Idunn Technologies Inc.的商业成功产生重大有益影响。

Using funding provided by the NSERC Engage and Engage Plus grants, we have screened a library of plantextracts (PEs) for extracts that can delay chronological aging of the yeast Saccharomyces cerevisiae. Thelibrary was provided by Idunn Technologies Inc., a company in the Montreal area. Our initial screen hasrevealed 6 PEs that increase yeast chronological lifespan to a significantly greater extent than any of thepresently known longevity-extending chemical compounds. We demonstrated that each of the 6 initiallydiscovered PEs is a geroprotector which elicits a hormetic stress response, affects a distinct set oflongevity-defining cellular processes, and slows yeast chronological aging through different signaling pathwaysand protein kinases that converge into an evolutionarily conserved network. Our recent screen of the library ofPEs provided by Idunn Technologies Inc. has revealed 15 other extracts that delay yeast chronological aging.With the present research proposal, we seek the CRD Grant for the period of 3 years. The proposed here CRDproject will: 1) identify chemical compounds responsible for the delay of aging by each of the 21 PEs wediscovered; 2) assess how the 15 recently discovered aging-delaying PEs influence a distinct set oflongevity-defining cellular processes; 3) investigate how the 15 recently discovered aging-delaying plantextracts impact a longevity-defining network of signaling pathways and protein kinases; and 4) examine ifsome combinations of the 21 PEs may have additive or synergistic effects on the aging-delaying efficiencies ofeach other. The proposed here research project will: 1) advance current understanding of mechanismsunderlying the complexity of biological aging; 2) stimulate professional development of two graduate students;3) enable to develop new formulations of natural health products with the maximal aging-delaying andlifespan-extending effects; 4) give Idunn Technologies Inc. access to the unique knowledge, expertise andeducational resources available in our laboratory at Concordia University; and 5) have a major beneficialimpact on the commercial success of Idunn Technologies Inc.