Comparative Bioenergetics of Aging

项目摘要 位于伯明翰的亚拉巴马大学（UAB）提议在2013年更新内森·肖克卓越中心。 衰老的基础生物学集中于比较生物能量学和衰老。能量学是全面的 为此目的，将其定义为研究收购的原因，机制和后果， 代谢能的储存和利用。比较能量学是对代谢过程的研究， 多个尺度和多个物种，在这种情况下，因为它涉及到健康和老龄化。近世纪的 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、代谢信号传导和营养反应。的双重目标 该中心将1）比以前更深入和详细地探索复杂的关系 在细胞和有机体能量学之间，以及它们与整个有机体的能量学、健康和 老化，以及2）在评估中提供定量的、最先进的技术和新的方法 和生物能量学的分析。为了实现这些目标，我们将 继续提供三个研究核心。1)比较有机能量学核心（Comparative Organismal Energetics Core） 有机核心）将提供专业知识和尖端的指导和方法，以确定 完整的整体动物能量平衡（摄入，同化和支出）和身体组成，包括 各种物种的活动物中白色和棕色脂肪组织的区域分布，包括蠕虫， 苍蝇、鱼、老鼠或其他哺乳动物，在不同的温度或活动制度。2)比较 线粒体健康评估核心（又名Mitmetabolism Core）将提供综合、定量 线粒体功能分析在细胞器水平，细胞，或组织的传统和新兴的 动物模型，包括靶向代谢组学、线粒体自噬评估和氧化应激。 线粒体-核交换模型也将可用于进行评估细胞增殖的实验。 mtDNA变异对生物能量学的贡献。3)比较数据分析核心（Comparative Data Analytics Core）分析 核心）将提供创新的分析方法，以数据集连接比较能量学， 健康和长寿。 有了这些研究核心加上行政计划丰富的核心（管理核心）和研究 发展核心（RDC），我们的目标是：1）促进假设驱动的研究和利用这些技术 在全国范围内开展基础老龄化研究的新项目、互动和合作; 2）培养有意义的 UAB内部以及整个地区和国家的研究者之间的新型互动;以及3）提供 通过智力资源向初级研究人员提供资源、教育、培训和指导， 研究中心将开发的基础设施。

Project Summary The University of Alabama at Birmingham (UAB) proposes to renew a Nathan Shock Center of Excellence in the Basic Biology of Aging focused on comparative bioenergetics 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 possible the complex relationship among cellular and organismal energetics and their relationship to whole organisms' energetics, health, and aging, and 2) provide quantitative, state-of-the-art technologies and novel methodologies in the assessment and analysis of bioenergetics to the geroscience community at large. In pursuit of these objectives, we will continue to provide three Research Cores. 1) The Comparative Organismal Energetics Core (a.k.a. Organismal Core) will provide expertise and cutting-edge instruction and methodology for determining complete whole-animal energy balance (intake, assimilation, and expenditure) and body composition, including regional distribution of white and brown adipose tissue, in living animals of various species, including worms, flies, fish, mice, or other mammals, under diverse temperature or activity regimes. 2) The Comparative Mitochondrial Health Assessment Core (a.k.a. Mitometabolism Core) will provide integrated, quantitative mitochondrial functional 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 also will be available to enable experiments that evaluate the contribution of mtDNA variation to bioenergetics. 3) The Comparative Data Analytics Core (a.k.a. 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 Program Enrichment Core (Admin Core) and Research Development Core (RDC), we aim to: 1) facilitate hypothesis-driven research and leverage these technologies into new projects, interactions, and collaborations nationwide in basic aging research; 2) foster meaningful novel interactions among investigators within UAB and across the region and country; and 3) provide resources, education, training, and direction to junior investigators through the intellectual resources and research infrastructure the Center will develop.