Metabolomics of Aging

衰老代谢组学

• 批准号: 8628376
• 负责人: Sun Hee Yim
• 金额: $ 16.22万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-30 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8628376
• 关键词: Address; Affect; Age; Age-Months; Aging; Aging-Related Process; Animal Model; Animals; Area; Basic Science; Biological; Biological Process; Body Fluids; Brain; Caloric Restriction; Cell Culture System; Cell Line; Cells; Chemicals; Clinical; Clinical Research; Collaborations; Complex; Data; Development; Disease; Embryo; Environment; Environmental Risk Factor; Fibroblasts; Gene Expression Profile; Genes; Genetic; Genome; Genomics; Goals; Human; Institutes; Kidney; Life; Liver; Longevity; Lung; Mammals; Maps; Marker Discovery; Metabolic; Metabolic Pathway; Methods; Mole Rats; Molecular; Molecular Biology; Mus; Muscle; Organism; Pathway interactions; Pharmaceutical Preparations; Phenotype; Physiological; Post-Translational Protein Processing; Process; Property; Proteome; Proteomics; Quality of life; Reporter; Research; Rodent; Rodent Model; Sampling; Sensitivity and Specificity; Serum; Sirolimus; Stress; System; Techniques; Technology; Testing; Tissues; Transcriptional Regulation; Urine; Whole Organism; Yeasts; age group; age related; animal tissue; candidate marker; computerized tools; environmental change; human disease; improved; in vivo; interest; loss of function; metabolomics; mouse model; public health relevance; response; signature molecule; small molecule; tool; transcriptomics

Project Summary Aging is a universal and fundamental biological process from yeast to humans. It is known that larger animals live longer and that there is an association between the aging process and the metabolic rate. Even though aging is not defined as a "condition to be treated" by the US Federal Drug Administration, it is the most prevalent disease-related state that affects every human being, and the majority of human diseases can be classified as the diseases of aging. In this regard, there are few biomedical goals as important as the understanding of aging. Longevity is a consequence of complex processes with contributions from both genetic and environmental factors. Genomic, transcriptomic, and proteomic research tools have been applied to understand aging and age-related diseases. Recently, metabolite profiling has been employed to investigate the dynamics of metabolic flux and interaction between genetic and environmental factors. Metabolite profiling offers the quantitative analysis of numerous endogenous small molecules and their interactions in response to physiological and environmental changes. Our research interests are in understanding dynamics of metabolites during the aging process, especially accumulation of molecular damage. The proposed study will employ metabolite profiling to test the concepts of 'cellular damage accumulation' during aging, characterize their identity, and understand the underlying mechanisms. Although the concept of age-associated damage accumulation is not new, previous advances in this area have been limited by technology. What were needed are methods that go to sufficient depth in characterizing cellular components, whereby detecting numerous damage forms. Advances in sensitivity and specificity of this technology made it possible to analyze changes in more than 15,000 compounds from minimal amounts of tissues. Advanced technology, sensitivity of metabolite profiles and collaboration with Dr. Clary Clish, Director of Metabolite Profiling at the Broad Institute, will allow us to test questions which could not be addressed previously. Using this rapidly developing approach, we propose to advance the area of metabolomics of aging. We will be test the hypotheses that there are metabolites that change as a function of age, that they can be detected and analyzed by advanced metabolite profiling methods, and that they correlate with the development of age- related disease and treatments known to extend lifespan. To address these questions, we will characterize metabolites in rodent models characterized by differences in lifespan, identify candidate markers of aging, determine their basic properties, and characterize them in long-lived animal models.

项目概要 衰老是从酵母到人类的普遍且基本的生物过程。众所周知，体型较大的动物 寿命更长，并且衰老过程与新陈代谢率之间存在关联。虽然 美国联邦药物管理局并未将衰老定义为“需要治疗的病症”，它是最重要的 影响每个人的流行疾病相关状态，大多数人类疾病都可以通过 归类为衰老性疾病。在这方面，很少有生物医学目标比 对衰老的理解。长寿是复杂过程的结果，遗传和基因的贡献 和环境因素。基因组、转录组和蛋白质组研究工具已应用于 了解衰老和与年龄相关的疾病。最近，代谢物分析已被用来研究 代谢通量的动态以及遗传和环境因素之间的相互作用。代谢物分析 提供众多内源性小分子及其相互作用的定量分析 生理和环境的变化。我们的研究兴趣是了解动态 衰老过程中的代谢产物，特别是分子损伤的积累。拟议的 研究将采用代谢物分析来测试“细胞损伤积累”的概念 老化，表征其身份，并了解潜在机制。虽然这个概念 与年龄相关的损伤累积并不新鲜，该领域之前的进展受到以下因素的限制： 技术。我们需要的是能够足够深入地表征细胞成分的方法， 从而检测多种损坏形式。该技术的灵敏度和特异性方面的进步使得 可以从极少量的组织中分析 15,000 多种化合物的变化。先进的 技术、代谢物谱的敏感性以及与代谢物总监 Clary Clish 博士的合作 在布罗德研究所进行分析将使我们能够测试以前无法解决的问题。使用 通过这种快速发展的方法，我们建议推进衰老代谢组学领域的发展。我们将进行测试 假设代谢物会随着年龄的变化而变化，并且它们可以被检测到并 通过先进的代谢物分析方法进行分析，并且它们与年龄的发展相关 已知可延长寿命的相关疾病和治疗方法。为了解决这些问题，我们将描述 以寿命差异为特征的啮齿动物模型中的代谢物，识别衰老的候选标志物， 确定它们的基本特性，并在长寿动物模型中表征它们。