C. elegans testing program expansion: Healthspan focus

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。身体和认知 衰退限制了老年人及其照顾者的生活质量。老龄化是主要的风险因素，以及 可能导致癌症、糖尿病和神经退行性疾病，因此与衰弱作斗争 疾病是老龄化人口常见的健康负担。毫无疑问，促进健康 延缓衰老的衰老应该是当前医学研究的主要目标。 为了研究健康的衰老，已经使用了简单的动物模型，如线虫线虫。 提供对基因和化学化合物干预的分子洞察，这些干预可以调节 保守的衰老过程很可能在人类身上也有类似的作用。拟议工作的目标是 继续和扩大合作科学小组的努力，该小组涉及三个密切互动的 协调测试药物干预延长健康衰老能力的实验室 并促进线虫的长寿。这个整合的超级团队的一个特别重点是测试 针对线虫属天然变种集合的有希望的药物，这些变种加在一起代表着 人类群体中广泛的遗传异质性。我们的想法是，治疗可以赋予 在不同人群中取得积极成果将增加在以下方面有效的机会 更高级的生物体，将被建议作为临床前小鼠研究中测试的优先干预措施 可能还有未来的人体试验。 这一具体建议的重点是筛选测试化合物，以促进 一系列老年人健康状况良好的指标。我们将重点介绍与人类相似的措施 衰老：运动能力下降，对应激的抵抗力减弱，类心脏肌肉功能恶化， 肠道屏障功能的破坏，以及与年龄相关的色素在非分裂细胞中的积累。 我们的发现将与对同样的复合长寿干预措施的平行评估相结合， 这样我们就可以定义提高老年生活质量和功能的治疗方法，而不是 那些简单地延长寿命的东西。 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 有力地促进不同人群健康的干预措施，对 开发促进人类健康衰老的治疗方法。

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 used to provide 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 their 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 specific proposal is the screening of test compounds for the capacity to promote a range of indicators of strong health in older age. We will focus on measures with parallels to human aging: locomotory decline, diminished resistance to stress, deterioration of cardiac-like muscle function, disruption of intestinal barrier function, and accumulation of age-related pigments in non-dividing cells. Our findings will be integrated with parallel evaluation of the same compound interventions on longevity, so that we can define treatments that promote the quality and functionality of older age life, rather than those that simply extend life. 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.