MOUSE MODELS

项目总结(见说明)： 小鼠模型核心(核心B)将负责为该计划项目的研究人员提供实现其实验目标所需的组织和细胞。该计划项目中的实验重点是小鼠，既有自然衰老的小鼠，也有经过基因改造迅速老化的独特品系的小鼠，这将加快研究的步伐。将培育双突变小鼠、报告小鼠和一次加速一个组织衰老的小鼠的新品系，以解决首要问题--随机的内源性损伤是否通过细胞自主或非自主机制促进衰老？除了遗传方法外，还将在核心B中的小鼠身上进行治疗研究，以测试关于氧化应激、信号通路和成人干细胞磨损对衰老的贡献的具体假设。通过协调该核心内动物队列的创建和暴露研究，将有可能使方法和质量控制标准化，这将提高活体实验的重复性，最大限度地减少动物使用和成本，并显著提高量化衰老的分析方法(例如组织病理学和蛋白质组学)的灵敏度。此外，这个集中的核心支持一种综合的系统生物学方法来研究衰老，因为通过与每个其他项目和核心共享样本，将获得每个被研究动物的所有以下信息：生命统计数据、与衰老相关的症状开始时的年龄、器官功能障碍和组织病理学：核心B的ROS水平、线粒体功能、细胞死亡和衰老、受影响的细胞类型的识别：核心C氧化DNA损伤的水平：项目1核因子-kB的激活以及应对细胞损伤和炎症的信号：项目2成年干细胞功能：项目3

PROJECT SUMMARY (See instructions): The Mouse Models Core (Core B) will be responsible for providing the investigators of this Program Project with the tissues and cells necessary to achieve their experimental aims. Experiments in this Program Project focus on mice, both naturally aged mice and a unique strain of mice engineered to age rapidly, which will accelerate the pace of research. Novel strains of double mutant mice, reporter mice, and mice with accelerated aging of one tissue at a time will be bred to address the overarching question- does stochastic, endogenous damage promote aging via a cell autonomous or non-autonomous mechanism? In addition to the genetic approaches, treatment studies will be conducted on mice in Core B to test specific hypotheses about the contribution of oxidative stress, signaling pathways and adult stem cell attrition to aging. By coordinating the creation of animal cohorts and exposure studies within this Core, it will be possible to standardize methods and quality control, which will improve the reproducibility of in vivo experiments, minimize animal use and costs, and dramatically improve the sensitivity of analytical approaches to quantify aging (e.g. histopathology and proteomics). In addition, this centralized Core supports an integrated systems biology approach to the study of aging because all of the following information will be obtained for each animal studied via sharing specimens with each ofthe other projects and cores: Vital statistics, age at onset of aging-related symptoms, organ dysfunction and histopathology: Core B Level of ROS, mitochondrial function, cell death and senescence, identification of cell types affected: Core C Level of oxidative DNA damage: Project 1 Activation of NF-kB and signaling in response to cellular damage and inflammation: Project 2 Adult stem cell function: Project 3