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.

延长小鼠寿命的小分子的鉴定提供了新的见解