Center for Testing Potential Anti-Aging Interventions

潜在抗衰老干预测试中心

• 批准号: 10165431
• 负责人: RANDY STRONG
• 金额: $ 151.81万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-15 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10165431
• 关键词: Acarbose; Adult; Age; Aging; Biology of Aging; Body Temperature; Communities; Complement; Data; Data Coordinating Center; Data Display; Data Pooling; Data Set; Databases; Development; Disease; Dose; Elderly; Estradiol; Experimental Designs; Extensive Stage; Freezing; Future; Glycine; Growth; Hand Strength; Health; Health Sciences; Human; Individual; International; Intervention; Joints; Laboratories; Life; Link; Longevity; Mammals; Measures; Michigan; Mollies; Mus; New Agents; Outcome; Pathology; Pharmaceutical Preparations; Pharmacology; Pilot Projects; Policies; Preventive Medicine; Process; Progress Reports; Protocols documentation; Reading; Reproducibility; Research; Research Institute; Resources; Rotarod Performance Test; Schedule; Scientist; Sirolimus; Site; Specificity; Specimen; Standardization; System; Testing; Texas; The Jackson Laboratory; Tissue Sample; Tissues; Universities; Work; anti aging; comparative; data repository; experimental study; healthspan; innovation; insight; middle age; mouse model; phenome; pre-clinical; programs; response; sex; sexual dimorphism; small molecule; trait; translational research program; web site

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.

鉴定延长小鼠寿命的小分子提供了新的见解 哺乳动物的寿命确定机制，并可能为最终的基础奠定基础 人类的抗衰老疗法。 NIA干预测试计划（ITP）评估代理 提议通过衰老或延期延长鼠标寿命 疾病。来自研究的多个合作科学家提出的干预措施 社区在三个地点并行测试（密歇根大学杰克逊实验室 德克萨斯大学使用相同的标准化协议，并使用足够的数字 遗传性异构小鼠的遗传性小鼠可提供80％的功率来检测寿命的变化 在任何两个测试地点汇总数据之后，10％的性别。七十二个这样的寿命 实验涉及各种剂量的44种不同的剂，在前15个 ITP年。 37个实验涉及多剂量的比较测试 有效的代理，可变的起始年龄或替代给药时间表。重大影响 长寿在一个或两个性别中已被记录，然后确认为NDGA， 雷帕霉素，阿果霉和17-α-雌二醇（17AE2），具有显着（但目前未经证实） protandim，甘氨酸以及在临时分析中也注意到了canagliflozin的效果。寿命试验 现在正在为18个新代理商准备。 ITP生存结果还记录了寿命 从中年开始的三个特工的好处是：雷帕霉素，阿卡伯菌和17AE2。这 前五年期已经引入了ITP的三个新功能：加剧重点 健康结果（与人类健康有关的功能测试不一定与寿命有关） 协作互动计划，以提供ITP药物处理的小鼠的组织到开放的组织 成长的国际科学合作者网络以及公共访问的数据 由鼠标现象数据库托管在杰克逊的存储库和显示引擎 实验室。接下来的五年计划包括额外的寿命（“ I阶段”）试验， 详细的分析（“阶段II”）的代理人发现了寿命，数据的持续增长 健康成果，以及与科学家的合作工作，研究对假设的药物影响 老化的机制和与疾病的联系。德克萨斯州的研究，旨在完成和扩展 联合ITP发现将继续我们对性的年龄特异性和基础的研究 延长生命的药物的二态性。我们将继续对这些影响的影响 衰老小鼠的健康跨度和功能缺陷的药物。提出的工作应允许 ITP继续为哺乳动物衰老的生物学做出重大贡献。