MOUSE MODELS

项目总结（见说明）： 小鼠模型核心（核心B）将负责为本计划项目的研究者提供实现其实验目标所需的组织和细胞。该计划项目的实验重点是小鼠，包括自然衰老的小鼠和一种独特的小鼠品系，这些小鼠被设计成快速衰老，这将加快研究的步伐。新品系的双突变小鼠、报告小鼠和一次一个组织加速老化的小鼠将被培育以解决首要问题-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中对小鼠进行治疗研究，以检验关于氧化应激、信号传导通路和成体干细胞磨损对衰老的贡献的特定假设。通过在该核心内协调动物队列和暴露研究的创建，将有可能实现方法和质量控制的标准化，这将提高体内实验的重现性，最大限度地减少动物使用和成本，并显着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，该集中核心支持衰老研究的综合系统生物学方法，因为通过与其他项目和核心共享样本，将获得每只研究动物的以下所有信息：生命统计数据、衰老相关症状发作时的年龄、器官功能障碍和组织病理学：核心B ROS水平、线粒体功能、细胞死亡和衰老、受影响细胞类型的鉴定：核心C氧化DNA损伤水平：项目1 NF-kB的激活和信号传导对细胞损伤和炎症的反应：项目2成体干细胞功能：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