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

秀丽隐杆线虫干预测试计划：调节健康、长寿和衰老标志的干预措施

• 批准号: 10515852
• 负责人: MONICA A. DRISCOLL
• 金额: $ 62.96万
• 依托单位: RUTGERS, THE STATE UNIV OF N.J.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-15 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10515852
• 关键词: Acceleration; Age; Aging; American; Animal Model; Biological Assay; Biological Models; Biology of Aging; Caenorhabditis; Caenorhabditis elegans; Caregivers; Chemicals; Chronic Disease; Chronology; Clinical Research; Clinical Sciences; Collection; Communities; Data; Data Set; Databases; Dementia; Deterioration; Diabetes Mellitus; Disease; Disease susceptibility; Economics; Elderly; Engineering; Evaluation; Gene Deletion; Gene Expression Regulation; Genes; Genetic; Genetic Drift; Genetic Heterogeneity; Goals; Health; Healthcare Systems; Heart; Heterogeneity; Human; Impaired cognition; Impairment; Individual; Intervention; Laboratories; Lead; Life; Link; Literature; Locomotion; Longevity; Maintenance; Malignant Neoplasms; Medical Research; Metabolism; Mitochondria; Modeling; Mus; Nematoda; Neurodegenerative Disorders; Oregon; Outcome; Pathway interactions; Pattern; Pharmacology; Population; Population Heterogeneity; Privatization; Process; Quality of life; Reporting; Reproducibility; Research; Resistance; Resolution; Risk; Risk Factors; Science; Signal Transduction; Site; Societies; Stress; System; Systems Analysis; Testing; Translating; Translations; Validation; Variant; Virus Diseases; Work; age related; anti aging; base; design; efficacy testing; experimental study; genome editing; healthspan; healthy aging; human old age (65+); improved; innovation; intervention program; mortality; novel; pre-clinical; pre-clinical research; programs; proteostasis; response; screening; success; therapy development; transcriptome sequencing; whole genome

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.

秀丽隐杆线虫干预检测项目更新--项目概要 与人类衰老相关的健康挑战对社会造成巨大影响。 老年人及其护理人员的生活质量是导致以下情况的主要风险因素和可能原因。 毫无疑问，癌症、糖尿病和神经退行性疾病与促进健康老龄化有关。 延长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进展，这门科学即将成为现实。 转化为临床前和临床科学。 简单的动物模型，例如线虫秀丽隐杆线虫，是这一成功的核心。 许多调节衰老过程的基因和化合物干预措施可能在以下方面发挥类似作用： 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，它们协调测试药理学干预措施的效果 延长线虫健康衰老和促进寿命的能力是这种综合的特别强调。 超级小组将在一系列秀丽隐杆线虫属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。 在不同人群中获得积极结果的治疗将有更大的机会获得 对人类有效。 该具体提案的重点是筛选具有促进长寿能力的测试化合物 我们将通过公共访问门户考虑化合物的遗传多样性测试集。 我们的实验室也将开发和利用文献中的领先技术以及高通量化学筛选技术来延长寿命。 测试编码蛋白质稳态、新陈代谢、 不同遗传背景下的细胞间信号传导和线粒体维持以进行化合物评估。 通过创造在衰老的保守特征中受损的“危险”菌株，我们可能会增加 我们将扩大对最有效机制的了解。 总的来说，我们将参与一个独特的团队项目，该项目有能力 定义药物干预措施，大力促进不同人群的健康寿命， 对开发促进人类健康衰老的疗法的影响。