Center for Testing Potential Anti-Aging Interventions

描述（由申请人提供）：拟议的圣安东尼奥老化干预测试中心将建立在UTHSCSA在老化生物学研究方面的公认优势基础上。这些包括用于测量长寿，生活史特征和表征在广泛的遗传，药理学和营养干预下小鼠的病理学和其他衰老生物标志物的既定核心。 该中心的三个主要目标是：（1）评估假设延缓衰老和延长啮齿动物寿命的化合物;（2）确定那些可能有害或无效的干预措施;（3）通过此类试验测试有关衰老机制的假设。 为实现这些目标，我们提出以下具体目标： 1.与其他中心和NIA工作人员一起选择化合物，以测试其促进健康老龄化的能力。 2.进行药代动力学和毒理学研究，以确定I期和II期寿命研究的适当起始剂量，并确定幼龄动物的剂量是否适用于老龄动物。 3.使用遗传异质性4向杂交小鼠进行I期寿命研究，每种选定的化合物以两种剂量给药。 4.对I期研究中的所有小鼠进行大体临终病理学分析，并对I期研究中的选定小鼠和II期研究中的所有小鼠进行综合临终病理学分析。 5.对I期研究显示具有潜在抗衰老作用的所有化合物进行II期长寿和年龄敏感性性状测定。

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.