Caenorhabditis Intervention Testing Program (CITP) at the University of Oregon

项目摘要 与人类老龄化相关的健康挑战给我们的社会带来了巨大的损失。物理和 认知能力下降限制了老年人及其照顾者的生活质量。老龄化是主要原因 癌症、糖尿病和神经退行性疾病的危险因素和可能的原因，因此 与衰弱的疾病作斗争是老龄化人口的共同健康负担。如果没有 问题是，促进健康老龄化和延缓衰老应该是一个主要的 当前医学研究的目标。 为了研究健康的衰老，线虫等简单的动物模型 提供了对基因和化学化合物干预的分子洞察力 这可以调节保守的衰老过程，很可能在人类身上也有类似的作用。的目标是 拟议的工作是继续并扩大一个合作科学小组的工作，该小组包括 三个密切互动的实验室，他们协调测试药物干预对 延长线虫健康衰老和延长寿命的能力。这方面的一个特别强调 整合的超级小组将在一系列天然变种上测试有前景的药物 线虫属，它们共同代表着广泛的遗传异质性。 人类人口。这个想法是，通过各种不同的治疗方法带来积极的结果 种群在高等生物体中有效的机会将增加，并将 建议作为优先干预措施在临床前小鼠研究中进行测试，并可能在未来 人体试验。 这项建议的重点是评估CITP之前的多样性小组 建立调查菌株内和菌株间变异的来源，包括可能的食物 通过化合物相互作用，并使用一组基因表达标记来识别基因 作为在测试阶段确定的化合物的作用目标的途径 项目。 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 药理学干预措施有力地促进了不同类型的人的健康 这对促进人类健康老龄化的治疗方法的发展具有重要意义。

Project Summary Health challenges linked to human aging take a tremendous toll on our 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, and thus struggle with debilitating disease is a common health burden for the aging population. Without question, the promotion of healthy aging with extended resistance to decline should be a major objective of current medical research. To investigate healthy aging, simple animals models such as the nematode C. elegans have been studied, providing molecular insights into the genes and chemical compound interventions that can modulate conserved aging processes 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 the ability to extend healthy aging and promote longevity in nematodes. A specific emphasis of this integrated super-group is to test promising drugs 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 efficacious in higher organisms and will be suggested as priority interventions for testing in pre-clinical mouse studies and possibly future human trials. The emphasis of this proposal is to evaluate the diversity panel that the CITP has previously established to investigate sources of within and between strain variation, including possible food by compound interactions, and to use a panel of gene expression markers to identify genetic pathways that serve as targets of action for compounds identified during the testing phase of the project. 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.