Core Facility for Aged Rodents

摘要 CFAR，老年啮齿动物的核心设施，一直是密歇根大学克劳德的一个主要特点 胡椒中心自1989年成立以来。CFAR将继续服务于Pepper Center的需求 通过四个具体目标的研究。目标1：我们将继续开展前五年开始的工作， 四种小鼠：（a）缺乏PAPP-A的小鼠，PAPP-A是一种控制IGF-1可用性的蛋白酶;（B）缺乏PAPP-A的小鼠 过表达突触融合蛋白-4，一种胰岛素敏感性的调节剂;（c）其中p16阳性（衰老）细胞 可以在成年时缺失;和（d）用利格列汀治疗的小鼠， 餐时血糖峰值目的2：我们将开发基于氨基酸限制的新小鼠模型， 遵循我们先前在给予有限量饮食的小鼠中证明的缓慢衰老和延迟疾病 蛋氨酸。目的3：我们将探讨青少年，成人和肝脏特异性生长激素反应的作用， 四种延长小鼠寿命的药物，特别是TOR抑制剂雷帕霉素，糖尿病药物阿卡波糖， 非女性化类固醇17-α-雌二醇和抗炎剂NDGA。目标4：我们将选择一个或 每年两个新的小鼠模型，通过与UM科学家，试点项目获奖者， 其他研究型大学的同事，对与生物学相关的问题进行初步发现研究， 衰老，强调以推迟晚年的方式改变新陈代谢和炎症的干预措施 疾病和残疾。

Abstract CFAR, the Core Facility for Aged Rodents, has been a major feature of the University of Michigan Claude Pepper Center since its inception in 1989. CFAR will continue to serve the needs of Pepper Center investigators through four Specific Aims. Aim 1: We will continue work initiated in the previous five years on four varieties of mice: (a) Mice lacking PAPP-A, a protease that controls IGF-1 availability; (b) Mice overexpressing Syntaxin-4, a modulator of insulin sensitivity; (c) Mice in which p16-positive (senescent) cells can be pharmacologically deleted at adult ages; and (d) Mice treated by linagliptin, a modulator of post- prandial glucose spikes. Aim 2: We will develop new mouse models based on amino acid restriction, which follows our previous demonstration of slow aging and delayed disease in mice given limiting amounts of dietary methionine. Aim 3: We will explore the role of juvenile, adult, and liver-specific growth hormone responses to four drugs that extend mouse lifespan, specifically the TOR inhibitor rapamycin, the diabetic drug acarbose, the non-feminizing steroid 17-α-estradiol, and the anti-inflammatory agent NDGA. Aim 4: We will select one or two new mouse models per year, through collaboration with UM scientists, pilot project awardees, and colleagues at other research universities, for initial discovery research on questions related to the biology of aging, emphasizing interventions that alter metabolism and inflammation in ways that postpone late life illnesses and disabilities.