Comparative Bioenergetics of Aging

项目摘要 阿拉巴马大学伯明翰分校(UAB)提议更新内森休克卓越中心 《衰老基础生物学》侧重于比较生物能量学和衰老。能量学是全面的 为此目的定义为研究收购的原因、机制和后果， 可代谢能量的储存和利用。比较能量学是对人体代谢过程的研究 多个规模和跨多个物种，在这种情况下，因为它与健康和老龄化有关。近一个世纪以来 衰老研究强化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、代谢信号和营养反应失调。的双重目标 该中心将比以前更深入和详细地探索复杂的关系 细胞和有机体能量学及其与整个有机体的能量学、健康和 老龄化，以及2)在评估中提供量化的最先进的技术和新的方法 以及对整个老年科学界的生物能量学分析。为了实现这些目标，我们将 继续提供三个研究核心。1)比较组织能量学核心(又名： 有机体核心)将提供专业知识和尖端指导和方法，以确定 完整的全动物能量平衡(摄入、同化和消耗)和身体组成，包括 白色和棕色脂肪组织在包括蠕虫在内的各种活动物中的区域分布， 苍蝇、鱼、老鼠或其他哺乳动物，在不同的温度或活动状态下。2)比较 线粒体健康评估核心(又名有丝分裂代谢核心)将提供综合的、定量的 传统的和新兴的线粒体在细胞器、细胞或组织水平的功能分析 动物模型，包括靶向代谢组学、有丝分裂吞噬评估和氧化应激。 线粒体-核交换模型也将可用于评估 线粒体DNA变异对生物能量学的贡献。3)比较数据分析核心(又名分析 CORE)将为将比较能量学与有机学联系起来的数据集提供创新的分析方法 健康长寿。 有了这些研究核心加上行政程序丰富核心(管理核心)和研究 开发核心(RDC)，我们的目标是：1)促进假设驱动的研究并利用这些技术 成为全国基础老龄化研究的新项目、互动和合作；2)促进有意义的 UAB内部以及整个区域和国家的调查人员之间的新互动；以及3)提供 资源、教育、培训和指导，通过智力资源和 该中心将发展研究基础设施。

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.