Caenorhabditis Intervention Testing Program at Oregon

俄勒冈州小杆线虫干预试验计划更新-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利用我们提供的非常高的时间分辨率， 自动化生命周期方法，以扩展我们现有的分析框架， 老龄化率的变化，使用更一般的统计模型，允许死亡率的变化 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， 非常适合复合干预。此外，我们将通过使用RNA- seq识别延长寿命化合物靶向的遗传途径，并了解 分子系统在以后的生命中维持早期生命功能，作为健康老龄化的标志。映射这些 对已知哺乳动物遗传调节系统的改变将使我们能够确定哪些干预措施是有效的。 最有可能作为快速翻译的目标。 总的来说，我们将参与一个独特的团队项目，该项目具有定义药理干预的能力 这有力地促进了不同人群的健康，对发展产生了影响， 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.