Center for Testing Potential Anti-Aging Interventions

识别延长小鼠寿命的小分子为研究提供了新的见解 哺乳动物决定寿命的机制，并可能为最终 人类的抗衰老疗法。NIA干预测试计划(ITP)评估试剂 建议通过延缓衰老或延缓晚年寿命来延长小鼠的寿命 疾病。来自该研究的多位合作科学家提出的干预措施 社区同时在三个站点(密歇根大学杰克逊实验室)进行测试 和德克萨斯大学)，使用相同的标准化协议，并使用足够的数字 为检测小鼠寿命的变化提供80%的能力 在汇集了任何两个考点的数据后，男女都有10%的比例。这样的寿命是72岁 涉及44种不同药剂的不同剂量的实验已经在前15个月启动。 ITP的岁月。37项实验涉及多剂量的对比测试 有效的制剂，可变的开始年龄，或替代的剂量计划。对……的重大影响 一种或两种性别的长寿已经被记录下来，然后被证实为NDGA， 雷帕霉素、阿卡波糖和17-α-雌二醇(17aE2)，有显著意义(但目前未证实) Protandim、甘氨酸和在一项中期分析中还注意到了Canagliflzin的效果。寿命试验 目前正在招聘18名新代理商。ITP的生存结果也证明了寿命 三种药物的益处始于中年：雷帕霉素、阿卡波糖和17aE2。这个 在前五年期间，ITP引入了三个新特点：更加重视 健康结果(与人类健康相关的功能测试不一定与寿命挂钩)，a 协作性互动计划将来自ITP药物治疗小鼠的组织提供给开放的、 不断扩大的国际科学合作者网络，以及可公开访问的数据 由杰克逊酒店的鼠标表现组数据库托管的存储库和显示引擎 实验室。下一个五年计划包括额外的寿命(“第一阶段”)试验， 对被发现可延长寿命的药物进行详细分析(“第二阶段”)，数据持续增长 健康结果，并与科学家合作研究假设的药物影响 衰老机制和与疾病的联系。在德克萨斯州的学习，旨在补充和扩展 联合ITP的发现，将继续我们的研究年龄特异性和基础的性别 延年药的二形性。我们将继续对这些药物的影响进行临床前研究。 关于衰老小鼠的健康寿命和功能缺陷的药物。拟议的工作应该允许 ITP将继续为哺乳动物衰老生物学做出重大贡献。

Identification of small molecules that extend mouse lifespan provides new insights into mechanisms of longevity determination in mammals, and may lay the groundwork for eventual anti-aging therapies in humans. The NIA Interventions Testing Program (ITP) evaluates agents proposed 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 tested, in parallel, at three sites (Jackson Laboratories, University of Michigan and University of 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. Seventy-two such lifespan experiments, involving various doses of 44 distinct agents, have been initiated in the first fifteen years of the ITP. Thirty-seven experiments have involved comparative tests of multiple doses of effective agents, variable starting ages, or alternative dosing schedules. Significant effects on longevity, in one or both sexes, have been documented and then confirmed for NDGA, rapamycin, acarbose, and 17-α-estradiol (17aE2), with significant (but currently unconfirmed) effects also noted for Protandim, glycine and, in an interim analysis, canagliflozin. Lifespan trials are now underway for 18 new agents. ITP survival results have also documented longevity benefits from three agents started in middle-age: rapamycin, acarbose, and 17aE2. The previous five year period has introduced three new features to the ITP: increased emphasis on health outcomes (functional tests relevant to human health not necessarily linked to lifespan), a Collaborative Interactions Program to provide tissues from ITP drug-treated mice to an open, growing, international network of scientific collaborators, and a publicly accessible data repository and display engine hosted by the Mouse Phenome Database at the Jackson Laboratory. Plans for the next five-year period include additional lifespan ("Stage I") trials, detailed analyses ("Stage II") of agents found to increase lifespan, continued growth in data on health outcomes, and collaborative work with scientists to study drug effects on postulated aging mechanisms and links to disease. Studies at Texas, aimed to complement and extend joint ITP discoveries, will continue our research on the age specificity of and basis for the sexual dimorphism of life-extending drugs. We will continue pre-clinical work on the effects of these agents on healthspan and functional deficits in aging mice. The work proposed should allow the ITP to continue making major contributions to mammalian aging biology.