Sex hormones and arthritis in a long lived animal model

描述(由申请人提供)：阿拉巴马大学伯明翰分校(UAB)建议建立一个内森·休克衰老基础生物学卓越中心，专注于比较能量学和衰老。为此目的，能量学被全面定义为研究可代谢能量获取、储存和利用的原因、机制和后果。比较能量学是在多个尺度和跨多个物种的代谢过程的研究，在这种情况下，它与健康和衰老有关。近一个世纪的衰老研究加强了能量学与衰老之间的联系。用现代术语来说，这种联系被具体化为线粒体功能失调、代谢信号和营养反应。该中心的双重目标将是(1)探索 比以前更深入和详细地研究细胞和生物能量学之间的复杂关系及其与健康和衰老的关系，以及(2)向广大基础衰老研究界提供在能量学评估和分析方面的量化、最先进的技术和新的方法。为了追求这些目标，我们建议开发三个研究核心。首先，比较组织能量学核心将提供专业知识和前沿指导和方法，以确定完整的整体动物能量平衡(摄取、同化、消耗)和身体成分，包括白色和棕色脂肪组织的区域分布，不同物种的活动物，包括苍蝇、鱼、老鼠 或其他哺乳动物，在任何环境温度或活动状态下。其次，比较线粒体健康评估核心将为传统和新兴动物模型提供细胞器、细胞或组织水平的综合、定量的能量分析，包括靶向代谢组学、有丝分裂评估和氧化应激。线粒体-核交换模型也可用于评估线粒体DNA变异对生物能量学的贡献的实验。第三，比较数据分析核心将为将比较能量学与生物体健康和寿命联系起来的数据集提供创新的分析方法。通过这些研究核心加上行政和研究开发核心，我们的目标是：(I)促进假说驱动的研究，并将这些技术运用到全国基础老龄化研究的新项目、互动和合作中；(Ii)促进UAB内部以及整个地区和国家的研究人员之间有意义的新颖互动；以及(Iii)通过中心将开发的智力资源和研究基础设施，为初级调查人员提供资源、教育、培训和指导。总而言之，这些核心和为该中心聚集的优秀调查人员队伍将为UAB和其他地方的新老调查人员提供独特的专业知识和新的合作机会。

DESCRIPTION (provided by applicant): The University of Alabama at Birmingham (UAB) proposes to establish a Nathan Shock Center of Excellence in the Basic Biology of Aging focused on comparative energetics and aging. Energetics is comprehensively defined for this purpose as the study of the causes, mechanisms, and consequences of the acquisition, storage, and utilization of metabolizable energy. Comparative energetics is the study of metabolic processes at multiple scales and across multiple species, in this case as it relates to health and aging. Nearly a century of aging research has reinforced the link between energetics and aging. In modern terms this link is reified as dysregulated mitochondrial function, metabolic signaling, and nutrient responsiveness. The twin objectives of the Center will be to (1) explore in greater depth and detail than previously the complex relationship among cellular and organismal energetics and their relationship to health and aging, and (2) provide quantitative, state-of-the-art technologies and novel methodologies in the assessment and analysis of energetics to the basic aging research community at large. In pursuit of these objectives, we propose developing three research cores. First, the Comparative Organismal Energetics Core will provide expertise and cutting edge instruction and methodology for determining complete whole animal energy balance (intake, assimilation, expenditure) and body composition, including regional distribution of white and brown adipose tissue, in living animals of various species including flies, fish, mice or other mammals, under any ambient temperature or activity regime. Second, the Comparative Mitochondrial Health Assessment Core will provide integrated, quantitative energetics analysis at the level of the organelle, cell, or tissue for both traditional and emerging animal models, including targeted metabolomics, assessment of mitophagy, and oxidative stress. Mitochondrial-nuclear exchange models are also available to enable experiments that evaluate the contribution of mtDNA variation to bioenergetics. Third, the Comparative Data Analytics Core will provide innovative analytic approaches to data sets linking comparative energetics to organismal health and longevity. With these research cores plus the administrative and research development core, we aim to: (i) facilitate hypothesis-driven research and leverage these technologies into new projects, interactions, and collaborations nationwide in basic aging research; (ii) foster meaningful novel interactions among investigators within UAB and across the region and country; and (iii) provide resources, education, training, and direction to junior investigators through the intellectual resources and research infrastructure, the Center will develop. In sum, these cores and the outstanding cohort of investigators assembled for this Center will provide unique expertise and novel collaborative opportunities for new and established investigators at UAB and beyond.