Caenorhabditis Intervention Testing Program at Oregon

俄勒冈州线虫病干预检测项目更新--项目摘要 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利用我们的 自动生命周期方法，以扩展我们现有的分析框架，以包括以下分析 使用考虑死亡率变化的更一般的统计模型来研究老龄化速率的变化 在一个人的一生中。这种方法提供了一个独特的假设检验框架，尤其是 非常适合于复合干预。此外，我们将通过使用RNA来增强我们的翻译能力- SEQ以识别延长寿命的化合物所针对的遗传途径并了解哪些 分子系统在晚年维持生命早期的功能，作为健康衰老的标志。绘制这些地图 对已知哺乳动物基因调控系统的改变将使我们能够确定哪些干预措施 最有可能成为快速翻译的目标。 总体而言，我们将参与一个独特的团队项目，该项目有能力定义药理学干预 这有力地促进了不同人群的强大健康寿命，对 促进人类健康衰老的疗法。

Caenorhabditis Intervention Testing Program Renewal at Oregon—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 animal 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 to capitalize upon the very high temporal resolution provided by our automated lifespan approach to expand upon our existing analytical framework to include an analysis of variation in rates of aging using more general statistical models that allow for changes in the rate of mortality over an individual’s lifespan. This approach provides a unique hypothesis testing framework that is particularly well suited for compound interventions. In addition, we will build upon our translational capacity by using RNA- seq to identify genetic pathways targeted by longevity-extending compounds and to understand which molecular systems maintain early-life function later in life as a hallmark of healthy aging. Mapping these changes onto known mammalian genetic regulatory systems will allow us to determine which interventions are most likely to serve as targets for rapid 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.