Laboratory for Anti-Geric Testing, Evaluation and Research

抗感冒测试、评估与研究实验室

• 批准号: 9899403
• 负责人: RICHARD A MILLER
• 金额: $ 78万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-15 至 2019-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9899403
• 关键词: Acarbose; Age; Aging; Aspirin; Collaborations; Communities; Development; Disease; Dose; Drug effect disorder; Elderly; Estradiol; Evaluation Research; Health; Intervention; Laboratories; Longevity; Measures; Mediating; Meta-Analysis; Michigan; Mus; Pathology; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology; Physiological; Protocols documentation; Research; Scientist; Sirolimus; Site; Standardization; Statistical Data Interpretation; Testing; Texas; The Jackson Laboratory; Universities; experimental study; improved; middle age; programs; sex; trait; translational research program

Abstract The NIA Interventions Testing Program represents a multi-site translational research program to evaluate agents hypothesized to extend mouse lifespan by retardation of aging or postponement of late life diseases. Interventions proposed by multiple collaborating scientists from the research community are initially tested, in parallel, at three sites (Jackson Laboratories, Michigan and Texas), using identical, standardized protocols, and using sufficient numbers of genetically heterogeneous mice to provide 80% power for detecting changes in lifespan of 10%, for either sex, after pooling data from any two of the test sites. Forty such lifespan experiments, involving various doses of 25 distinct agents, have been initiated in the first nine years of the ITP. Significant effects on longevity, in one or both sexes, have been documented for 5 of the tested agents: aspirin, NDGA, rapamycin, Acarbose, and 17-α-estradiol. Initial lifespan trials are now underway for 8 agents, as well as comprehensive analyses of the effects of rapamycin, Acarbose, and NDGA on health and on cellular and physiological traits thought likely to mediate the beneficial effects seen. Plans for the next five year period include additional lifespan ("Stage I") trials, detailed analyses ("Stage II") of agents found to increase lifespan, and some increased emphasis on collaborations with other scientists skilled at evaluating traits related to health and disease or at testing ideas about mechanisms of drug action on aging. Each of the three ITP laboratories will bring special expertise to the effort: measures of age-sensitive traits at the Jackson Laboratory, pathology and statistical analysis at Michigan, and pharmacology at the University of Texas.

摘要 NIA干预测试计划代表了一个多站点转化研究计划，以评估 假设通过延缓衰老或延缓晚年疾病来延长小鼠寿命的药剂。 来自研究界的多位合作科学家提出的干预措施最初得到了测试， 平行地，在三个地点（杰克逊实验室，密歇根州和得克萨斯州），使用相同的标准化方案， 使用足够数量的遗传异质性小鼠，以提供80%的功效来检测 在合并任何两个试验中心的数据后，两种性别的寿命均为10%。40岁的寿命 在ITP的前九年，已经开始了涉及25种不同药剂的不同剂量的实验。 已记录5种受试药物对一种或两种性别的寿命有显著影响： 阿司匹林、NDGA、雷帕霉素、阿卡波糖和17-α-雌二醇。目前正在对8种药物进行初步寿命试验， 以及雷帕霉素、阿卡波糖和NDGA对健康和细胞的影响的综合分析。 以及被认为可能介导所看到的有益效果的生理特征。未来五年计划 包括额外寿命（“第一阶段”）试验、发现可延长寿命的药剂的详细分析（“第二阶段”） 一些人越来越重视与其他擅长评估与以下方面相关的性状的科学家的合作： 健康和疾病或测试药物对衰老作用机制的想法。三个ITP 实验室将为这项工作带来特殊的专业知识：在杰克逊测量年龄敏感特征 密歇根大学的实验室、病理学和统计分析，德克萨斯大学的药理学。