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

炎干预检测项目更新--项目总结 与人类老龄化相关的健康挑战给社会带来了巨大的损失。身体和认知能力下降极限 老年人及其照顾者的生活质量。年龄增长是导致这种疾病的主要危险因素和可能原因。 癌症、糖尿病和神经退行性疾病。毫无疑问，促进健康老龄化 扩大对衰退和疾病的抵抗力应该是当前医学研究的主要目标。 幸运的是，衰老生物学领域已经取得了巨大的进步，科学有望成为 转化为临床前和临床科学。 简单的动物模型，如线虫秀丽线虫，一直是这一成功的核心。 许多调节衰老过程的基因和化学化合物干预很可能在 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，他们协调地测试他们的 延长线虫健康衰老和延长寿命的能力。这是一个特别强调的综合 超级小组将在线虫属的一系列自然变种上测试有前景的化合物， 它们共同代表了人类群体中广泛的遗传异质性。我们的想法是 在不同人群中产生积极结果的治疗方法将有更高的机会 对人类有效。 这一具体建议的重点是筛选能够促进长寿的测试化合物。 以及在基因多样性测试集上的健康状况。我们将通过公共访问门户网站考虑化合物，从 文献中的铅，以及来自高通量化学筛选的长寿。我们的实验室还将开发和 对编码蛋白质平衡、新陈代谢的基本执行因子的基因进行工程删除的测试效用 细胞间信号和线粒体在不同遗传背景下的维持，用于化合物评估。 通过创造在保守的衰老特征中受损的“处于风险”的菌株，我们可能会增加 确定抗衰老疗法。我们将扩大对最有效机制的理解 化合物，帮助他们的翻译。总体而言，我们将参与一个独特的团队项目，该项目有能力 定义在不同人群中强有力地促进健康的药理学干预措施， 对开发促进人类健康衰老的疗法的启示。

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.