Core D - Comparative Mitochondrial Health Assessment Core

核心 D - 比较线粒体健康评估核心

• 批准号: 10461873
• 负责人: Jianhua Zhang
• 金额: $ 21.49万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-15 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10461873
• 关键词: Adipose tissue; Aging; Bioenergetics; Biology; Cells; Cellular Structures; Chronic Disease; Communities; Complement; Complex; Consultations; DNA Damage; DNA Sequence; Data; Data Analyses; Development; Disease; Educational workshop; Ensure; Experimental Designs; Failure; Freezing; Funding; Genetic; Gerontology; Grant; Haplotypes; Health; Immune response; Inflammatory; Innate Immune Response; Islets of Langerhans; Kidney; Lead; Link; Longevity; Maintenance; Mass Spectrum Analysis; Measurement; Measures; Metabolic; Metabolic stress; Metabolism; Methodology; Methods; Mitochondria; Mitochondrial DNA; Modeling; Molecular; Mus; Nuclear; Organism; Oxidation-Reduction; Oxidative Stress; Pattern; Plasma; Process; Proteins; Protocols documentation; Publishing; Quality Control; Research; Research Personnel; Resistance; Role; Sampling; Scientist; Services; Shock; Signal Transduction; Structure; Sulfhydryl Compounds; Surveys; Techniques; Technology; Testing; Tissue Sample; Tissues; Training and Education; Work; Zebrafish; age related; comparative; follow-up; health assessment; healthy aging; indexing; interest; member; metabolomics; mitochondrial dysfunction; mitochondrial metabolism; novel; novel strategies; oxidized lipid; programs; response; tool; virtual

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.

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和代谢对健康衰老至关重要。 尽管生物能量学指标已经在广泛的衰老模型中进行了调查，但进一步整合 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 更好地理解健康老龄化。我们将推广我们已有的生物能量健康的新概念 在上一个资助期为年龄相关研究制定的。在比较线粒体健康中 评估核心(有丝分裂核心)既有先进的技术，也有成熟的技术 生物能量学/新陈代谢、线粒体遗传学、线粒体动力学/有丝分裂和氧化还原生物学将 被供养。用于评估细胞生物能量学的最新实验设计和方案 可以实现活的和冷冻的细胞/组织/生物体的衰老模型。线粒体动力学和 有丝分裂现象已被证明是健康寿命的关键，而这些缺陷会导致 功能失调的线粒体堆积。核心将提供科学和技术援助，以 测量线粒体质量控制的这些参数。线粒体核交换(MNX)小鼠 将提供给老龄化社区，以允许特定的线粒体DNA序列对 老化过程将独立于核贡献进行评估。须向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如下：)分子能量学分析 包括细胞、组织和小生物体的测量，以及我们开创的方法 类球形细胞结构和复杂的多细胞结构，如胰岛、血管段 和脂肪组织，以及靶向代谢组学的补充方法。新奇的技术 评估冷冻组织将极大地扩展我们与UAB以外的调查人员合作的能力。2.)最新情况- ART技术能够实现相对有丝分裂和线粒体动力学，这是线粒体健康的关键， 线粒体质量控制与生物能量学参数的整合。这将是更远的 通过与分析核心的交互而得到加强。3.)线粒体核交换(MNX)模型 单倍型和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.)虚拟和湿实验室工作坊教育计划，以及 磋商。