Preclinical Discovery Core

旨在阐明作用机制或建立概念验证的临床前研究 动物模型中的功能促进疗法(FPT)的关键是根据测量 FPTS对全身和局部骨骼肌质量、肌力学和肌力的影响 表现、能量、血液流动和身体机能。基于对核心用户的调查，以及 经与兽医学会咨询委员会协商，执行委员会建立了小动物资源核心 (SARC)在OAIC第一个周期的第三年。来自SARC用户的其他反馈导致人们认识到 内科科学家，特别是在实验室动物方面经验有限的老年医生，需要大量的 指导选择合适的动物模型、遗传模型识别、结果选择、 实验设计和FPT研究的执行。因此，南盟核心的咨询作用 被扩展，核心被重新命名为临床前发现核心(PDC)。 在最初短暂的筹资周期中，PDC支持了3个PES项目、2个REC项目和7个外部项目。这个 利用PDC基础设施进行的研究产生了17份同行评议的出版物，其中包括几份高质量的出版物 在主要期刊上发表的影响论文，包括PNAS(2篇论文)、细胞代谢(1篇论文)、血液(1篇论文)、 糖尿病(1篇论文)和衰老细胞(2篇论文)，以及842万美元的赠款资金。 PDC的具体目标是提供基础设施、咨询支持和标准化方法 评估全身和局部骨骼肌和脂肪质量、肌肉性能和能量学， 衰老和疾病的临床前模型中的代谢结果和身体功能。PDC将发展 新的非侵入性成像方法测量肌原纤维间隙、血流灌注、能量和再生 FPT作用的临床前模型。PDC将通过人员培训和培训实施严格的质量控制 肌肉性能和身体功能评估的标准化程序认证，并由 维护设备校准。 开发项目(DP3)将开发一种创新的非侵入性定量评估方法 肌原纤维间隙、肌肉灌注、能量学和肌肉摄氧量，使用7特斯拉磁铁 共振成像和光谱学。PDC推出了几项创新，包括：整合 用于提高核磁共振身体成分评估精度的新的T1和T2序列；岩心的耦合 具有能量消耗评估的人体热发生学.高灵敏度电机电子设备的集成 提高体外力量测量的精密度和准确度；提高握力的精确度 强度测量。PDC提供的高度专业化的服务和专业知识在 OAIC，是成功执行若干外部项目和OAIC项目的核心。

Preclinical studies aimed at elucidating the mechanism of action or establishing the proof-of-concept of function promoting therapies (FPTs) in animal models are predicated critically upon the ability to measure the effects of FPTs on whole body and regional skeletal muscle mass and quality, muscle mechanics and performance, energetics, blood flow, and physical function. Based upon surveys of core users, and in consultation with OAIC's Advisory Board, the Executive Committee established a Small Animal Resource Core (SARC) in year 3 of OAIC's first cycle. Additional feedback from the SARC users led to the recognition that the physician scientists, especially geriatricians with limited experience with laboratory animals, needed substantial guidance in the selection of appropriate animal model, genetic model identification, outcome selection, experimental design and the execution of FPT studies. Accordingly, the consultative role of the SARC core was expanded and the core was re-named the Preclinical Discovery Core (PDC). In its initial brief funding cycle, the PDC supported 3 PES projects, 2 REC project, and 7 external projects. The studies utilizing the PDC infrastructure have resulted in 17 peer-reviewed publications, including several high- impact publications in leading journals including PNAS (2 papers), Cell Metabolism (1 paper), Blood (1 paper), Diabetes (1 paper), and Aging Cell (2 papers), and $8.42 million dollars in grant funding. The specific aims of the PDC are to provide the infrastructure, consultative support, and standardized methods to assess whole body and regional skeletal muscle and fat mass, muscle performance and energetics, metabolic outcomes, and physical function in preclinical models of aging and illness. The PDC will develop novel non-invasive imaging methods to measure myofibrillar space, perfusion, energetics, and regeneration in preclinical models of FPT action. The PDC will implement rigorous quality control by personnel training and certification in standardized procedures for assessment of muscle performance and physical function, and by maintaining equipment calibration. The developmental project (DP3) will develop an innovative non-invasive method for quantitative assessment of myofibrillar space, muscle perfusion, energetics, and muscle oxygen uptake, using 7 Tesla magnetic resonance imaging and spectroscopy. The PDC has introduced several innovations, including: integration of new T1 and T2 sequences for improved precision of body composition assessment by NMR; coupling of core body thermogenics with energy expenditure assessment; integration of high sensitivity motor electronics to improve the precision and accuracy of ex-vivo strength measurements; and improving the precision of grip strength measurements. The highly specialized services and expertise offered by PDC is unique among OAICs, and central to the successful execution of several external and OAIC projects.