Caenorhabditis Intervention Testing Program: Interventions That Modulate Health, Longevity and Aging Hallmarks

小杆线虫病干预试验方案更新-项目摘要 与人类老龄化相关的健康挑战给社会带来巨大损失。身体和认知能力下降极限 老年人及其照顾者的生活质量。衰老是主要的风险因素，也是可能的原因， 癌症、糖尿病和神经退行性疾病。毫无疑问，促进健康老龄化， 对衰退和疾病的长期抵抗力应该是当前医学研究的一个主要目标。 幸运的是，在衰老生物学领域已经取得了巨大的进展，这门科学即将成为 转化为临床前和临床科学。 简单的动物模型，如线虫秀丽隐杆线虫，是这一成功的核心。 许多调节衰老过程的基因和化学化合物干预可能在衰老过程中起类似的作用。 人类拟议工作的目标是继续并扩大合作科学小组的努力 涉及三个密切互动的实验室，他们协调测试药物干预， 能够延长线虫的健康衰老和促进长寿。这一综合的具体重点 超级小组的任务是在一组小杆线虫属的天然变种上测试有希望的化合物， 它们共同代表了人类群体中广泛的遗传异质性。这个想法是 在不同人群中产生积极结果的治疗将有更大的机会 对人类有效。 这一具体建议的重点是筛选试验化合物以提高寿命的能力 和健康之间的关系。我们将通过公共访问门户网站考虑化合物， 铅在文献中，并从高通量化学筛选寿命。我们的实验室还将开发和 测试编码蛋白质稳定，代谢， 用于化合物评价的不同遗传背景中的细胞间信号传导和线粒体维持。 通过创造在老化的保守标志中受损的“风险”菌株，我们可能会增加 识别抗衰老疗法。我们将扩大对机制的了解， 帮助他们翻译。总的来说，我们将参与一个独特的团队项目，该项目具有以下能力： 确定药物干预措施，在不同人群中大力促进健康， 对促进人类健康衰老的疗法发展的意义。

Caenorhabditis Intervention Testing Program Renewal--Project Summary Health challenges linked to human aging take a tremendous toll on society. Physical and cognitive decline limit the quality of life for the elderly and their caregivers. Aging is the major risk factor for, and possible cause of, cancer, diabetes, and neurodegenerative disease. Without question, the promotion of healthy aging with extended resistance to decline and disease should be a major objective of current medical research. Fortunately, tremendous progress has been made in the biology of aging field and the science is poised to be translated into preclinical and clinical science. Simple animals models such as the nematode Caenorhabditis elegans have been at the heart of this success. Many genes and chemical compound interventions that modulate aging processes are likely to act similarly in humans. The goal of the proposed work is to continue, and expand, efforts of a co-operative scientific group involving three closely interacting laboratories who coordinately test pharmacological interventions for their ability to extend healthy aging and promote longevity in nematodes. A specific emphasis of this integrated super-group is to test promising compound on a collection of natural variants of the Caenorhabditis genus, which together represent the extensive genetic heterogeneity in the human population. The idea is that treatments that confer positive outcomes across a diverse population will have an increased chance of being effective in humans. The emphasis of this specific proposal is the screening of test compounds for the capacity to promote longevity and health across a genetically diverse test set. We will consider compounds via a public access portal, from leads in the literature, and from high throughput chemical screens for longevity. Our labs will also develop and test utility of engineered deletions of genes encoding fundamental executors of proteostasis, metabolism, intercellular signaling and mitochondrial maintenance in diverse genetic backgrounds for compound evaluation. By creating “at risk’ strains impaired in conserved hallmarks of aging, we might increase the dynamic range for identifying anti-aging therapies. We will expand understanding of mechanisms for the most effective compounds, aiding their translation. Overall, we will participate in a unique team project that has the power to define pharmacological interventions that robustly promote strong healthspan across a varied population, with implications for development of therapies that promote healthy human aging.