Center for Testing Potential Anti-Aging Interventions

描述(由申请人提供)：拟议的圣安东尼奥衰老干预测试中心将建立在UTHSCSA在衰老生物学研究方面公认的优势基础上。其中包括在广泛的遗传、药理和营养干预下测量小鼠寿命、生活史特征和表征病理和其他衰老生物标记物的已建立的核心。该中心的三个主要目标是：(1)评估被认为可以延缓啮齿动物衰老和延长寿命的化合物；(2)确定那些可能有害或无效的干预措施；以及(3)通过这样的试验测试关于衰老机制的假设。为实现这些目标，我们提出了以下具体目标： 1.与其他中心和NIA工作人员一起挑选化合物，以测试其促进健康衰老的能力。 2.进行药代动力学和毒理学研究，以确定第一阶段和第二阶段生命周期研究的适当起始剂量，并确定幼年动物的剂量是否适合老年动物。 3.使用遗传异质性的四方杂交小鼠进行第一阶段寿命研究，每种选定的化合物都有两种剂量。 4.对第一阶段研究中的所有小鼠进行大体临终病理分析，并对选定的第一阶段研究中的小鼠和第二阶段研究中的所有小鼠进行综合临终病理学分析。 5.对从第一阶段研究中发现的所有具有潜在抗衰老作用的化合物进行第二阶段长寿和年龄敏感特性测定。

DESCRIPTION (provided by applicant): The proposed San Antonio Center for Testing Aging Interventions will build upon the recognized strengths of UTHSCSA in biology of aging research. These include established cores for measuring longevity, life history traits and characterizing the pathologies and other aging biomarkers of mice under a wide spectrum of genetic, pharmacological and nutritional interventions. The three major goals of the center are: (1) to assess compounds that are hypothesized to slow aging and extend life span in rodents; (2) to identify those interventions that might be harmful or ineffective; and (3) to test hypotheses concerning mechanisms of aging through such trials. To achieve these goals, we propose the following specific aims: 1. To participate with other centers and NIA staff in the selection of compounds to be tested for their ability to promote healthy aging. 2. To perform pharmacokinetic and toxicological studies to determine appropriate starting doses for life-span studies in Phase I and II and for determining if doses in young animals are appropriate for older animals. 3. To perform Phase I life span studies, using genetically heterogeneous 4-way cross mice, with each selected compound at two doses. 4. To conduct gross end-of-life pathological analysis for all mice in Phase I studies and comprehensive end-of-life pathology for selected mice in Phase I and all mice in Phase II studies. 5. To conduct Phase II longevity and age-sensitive trait determinations for all compounds revealed from Phase I studies to have potential anti-aging action.