Core D - Comparative Mitochondrial Health Assessment Core

项目摘要-比较线粒体健康评估核心 维持正常的线粒体生物能量学和代谢对健康衰老至关重要。 尽管已经在广泛的老化模型中调查了生物能量度量，但是进一步整合生物能量度量是不可能的。 这些参数与线粒体质量控制机制和线粒体遗传学是必要的， 更好地了解健康老龄化。我们将扩展生物能量健康的新概念， 这是在上一个资助期内为与年龄有关的研究制定的。比较线粒体健康 评估核心（核分裂代谢核心）的最新技术和既定技术， 生物能量学/代谢、线粒体遗传学、线粒体动力学/线粒体自噬和氧化还原生物学将 被提供。用于评估各种细胞生物能量学的最先进的实验设计和方案 可以获得老化模型的活的和冷冻的细胞/组织/生物体。线粒体动力学和 线粒体自噬已被证明是健康寿命所必需的，这些缺陷导致 功能失调的线粒体的积累。核心将提供科学和技术援助， 测量线粒体质量控制的这些参数。线粒体核交换（MNX）小鼠 将提供给老年社区，以允许特定的线粒体DNA序列对老年人的贡献。 老化过程将独立于核贡献进行评估。向NIA提供的服务 正式成员和支持成员以及试点和可行性赠款获得者是：1。分子能量学分析， 包括细胞、组织和小生物体测量，包括我们在 球状细胞结构和复杂的多细胞结构如胰岛、血管段 和脂肪组织，以及补充靶向代谢组学的方法。新技术 评估冷冻组织将极大地扩展我们与UAB以外的研究人员合作的能力。2.）的情况。国家 ART技术能够实现比较线粒体自噬和线粒体动力学，线粒体健康的关键， 以及线粒体质量控制与生物能量参数的整合。这将进一步 通过与Analytics Core的交互得到加强。3.）第三章线粒体核交换（MNX）模型， 单体型分析和mtDAMP测量，以测试mtDNA序列对生物能量学的独特贡献 以及对年龄相关疾病的反应。4.）虚拟和湿实验室研讨会教育计划，以及 诊症计算

Project Summary – Comparative Mitochondrial Health Assessment Core The maintenance of normal mitochondrial bioenergetics and metabolism is essential for healthy aging. Although bioenergetic metrics have been surveyed in a broad range of aging models, further integration of these parameters with mitochondrial quality-control mechanisms and mitochondrial genetics is necessary for a better understanding of healthy aging. We will extend the new concept of bioenergetic health we have formulated in the previous funding period for age-related research. In the Comparative Mitochondrial Health Assessment Core (Mitometabolism Core) both state-of-the-art and established techniques in bioenergetics/metabolism, mitochondrial genetics, mitochondrial dynamics/mitophagy, and redox biology will be offered. State-of-the-art experimental design and protocols for assessing cellular bioenergetics in various live and frozen cells/tissues/organisms of aging models can be achieved. Mitochondrial dynamics and mitophagy have been shown to be essential for healthy lifespan, and deficiencies of these lead to accumulation of dysfunctional mitochondria. The Core will provide scientific and technical assistance to measure these parameters of mitochondrial quality control. The mitochondrial nuclear exchange (MNX) mice will be offered to the aging community to allow the contribution of specific mitochondrial DNA sequences to the process of aging to be assessed independent of the nuclear contribution. Services to be provided to NIA regular and supported members and pilot and feasibility grant awardees are: 1.) Molecular energetics analysis, including cellular, tissue, and small organism measurements and including approaches we have pioneered in spheroid-like cell structures and complex multi-cellular structures such as pancreatic islets, vessel segments and adipose tissue, and complementing approaches with targeted metabolomics. Novel techniques of assessing frozen tissues will vastly expand our ability to work with investigators outside UAB. 2.) State-of-the- art technologies to enable comparative mitophagy and mitochondrial dynamics, keys to mitochondrial health, and the integration of mitochondrial quality control with bioenergetic parameters. This will be further strengthened by interactions with the Analytics Core. 3.) Mitochondrial nuclear exchange (MNX) models, haplotyping, and mtDAMP measurements to test the unique contribution of mtDNA sequences to bioenergetics and the response to age-related disease. 4.) Virtual and wet lab workshop educational programs, as well as consultations.