Center for Testing Potential Anti-Aging Interventions

描述(由申请人提供)：NIA干预测试计划是一项多地点转化性研究计划，旨在评估假想通过延缓衰老或延缓老年疾病而延长小鼠寿命的药物。来自研究界的多名合作科学家提出的干预措施最初是平行测试的，网址为 三个地点(杰克逊实验室、密歇根和德克萨斯州)，使用相同的标准化方案，并使用足够数量的遗传异质小鼠，在汇集来自任何两个测试地点的数据后，提供80%的功率来检测寿命的变化，无论性别是10%。在ITP的头九年里，已经启动了40个这样的寿命实验，涉及25种不同剂量的不同药物。在被测试的5种药物中，有5种已被证明对寿命有显著影响，无论是一种还是两种：阿司匹林、脱氧核糖核酸、雷帕霉素、阿卡波糖和17-α-雌二醇。目前正在进行8种药物的初步寿命试验，以及对雷帕霉素、阿卡波糖和NDGA对健康的影响以及对细胞和生理特征的综合分析，这些特征被认为可能介导了所看到的有益效果。未来五年的计划包括更多的寿命试验(“第一阶段”)，对发现可以延长寿命的制剂进行详细分析(“第二阶段”)，以及更加重视与其他擅长评估与健康和疾病有关的特征或测试药物对衰老作用机制的想法的科学家的合作。这三个ITP实验室中的每一个都将为杰克逊实验室的年龄敏感特征测量、密歇根的病理学和统计分析以及德克萨斯大学的药理学带来专门的专业知识。

DESCRIPTION (provided by applicant): 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 sexe, 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 agent found to increase lifespan, and 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.