Core 2: Heterogeneity of Aging

核心2：老龄化的异质性

• 批准号: 10410541
• 负责人: Martin W Hetzer
• 金额: $ 20.98万
• 依托单位: SALK INSTITUTE FOR BIOLOGICAL STUDIES
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10410541
• 关键词: Address; Age; Aging; Algorithms; Artificial Intelligence; Biology of Aging; Cell Aging; Cell model; Cell physiology; Cells; Collaborations; Disease; Ensure; Epigenetic Process; Experimental Designs; Functional disorder; Generations; Genome; Goals; Heterogeneity; Human; Impairment; Individual; Investigation; Knowledge; Leadership; Machine Learning; Mass Spectrum Analysis; Measures; Methods; Modeling; Molecular; Mosaicism; Organ; Organelles; Organoids; Pathology; Process; Proteomics; Records; Research; Research Personnel; Research Project Grants; Research Support; Resolution; Resources; Role; Running; Services; Shock; Site; System; Techniques; Technology; Tissues; Training; Work; age related; aged; base; cell type; data acquisition; experience; functional decline; high resolution imaging; image processing; imaging modality; imaging system; innovation; instrumentation; metabolomics; multimodality; multiple omics; new technology; next generation sequencing; novel; protein function; sequencing platform; single cell sequencing; temporal measurement; transcriptomics; virtual

PROJECT SUMMARY – Heterogeneity of Aging Core In line with the pioneering work of Nathan Shock, it is clear that aged tissues accumulate cellular heterogeneity or mosaicism. This heterogeneity is likely a cause of aging due to impairments in both intercellular interactions and the coordination of tissue function. The Heterogeneity of Aging Core (Heterogeneity Core) within the San Diego Nathan Shock Center of Excellence in Basic Biology of Aging (SD-NSC) will enable investigators to probe the heterogeneity of aging over a broad range of scales (from molecules to organelles to single cells and tissues) by providing access to a diverse suite of state-of-the-art instrumentation and analytical technologies, as well as experienced Core staff. The Core will provide specific resources for studying key processes implicated in aging and disease at high resolution, including single-cell next-generation sequencing platforms, high-resolution imaging systems, and mass spectrometry approaches to measure proteomic and metabolomics signatures of aging in cells and tissues, with an emphasis on cell-cell heterogeneity and heterogeneity across tissues. These technologies are rapidly evolving and will continue to do so over the coming years. Utilizing established Core resources with proven track records for staying current with evolving technologies is the most effective way to ensure new innovations in analytical technologies are available to the greatest breadth of aging researchers. The Heterogeneity Core provides specific support for researchers in the aging field by: 1) providing access to specific scientific services, advice, and expertise, 2) developing and disseminating novel methods for correlative data acquisitions, and 3) running on-site and virtual training sessions. The Heterogeneity Core is a critical component in the pipeline of research resources that our SD-NSC will create. The value of this Core is bolstered by the generation of age-equivalent induced cell types and organoids by the Human Cell Models of Aging Core, and novel machine-learning capabilities in the Integrative Models of Aging Core. Together we will provide researchers in the basic biology of aging field with the resources necessary to make key discoveries into the mechanisms by which we age. The Heterogeneity Core will enable studies into the cell-cell and tissue heterogeneity of aging and, ultimately, the contributions and mechanisms by which heterogeneity causes the degeneration and dysfunction that characterizes aging.

项目摘要 - 衰老核心的异质性 与内森休克的开创性工作一致，很明显，老化的组织积累了细胞异质性 或镶嵌。这种异质性可能是由于两种细胞间相互作用的损害而导致衰老的原因 以及组织功能的协调。 SAN中老化核心（异质性核心）的异质性 迭戈·内森（Diego Nathan）衰老基本生物学卓越卓越中心（SD-NSC）将使研究人员能够 探测在广泛尺度上衰老的异质性（从分子到细胞器再到单细胞和 通过提供一套最先进的仪器和分析技术的潜水员套件，从组织） 以及经验丰富的核心人员。核心将为研究关键流程提供特定的资源 以高分辨率在衰老和疾病中实施，包括单细胞的下一代测序平台， 高分辨率成像系统以及测量蛋白质组学和代谢组学的质谱法 细胞和组织中衰老的特征，重点是细胞细胞异质性和异质性 组织。这些技术正在迅速发展，并将在未来几年继续这样做。利用 建立的核心资源和可靠的记录记录以保持不断发展的技术保持最新状态是最重要的 确保分析技术的新创新的有效方法可获得最大的广度 老化的研究人员。异质性核心为衰老领域的研究人员提供了特定的支持：1） 提供对特定科学服务，建议和专业知识的访问权，2）开发和传播新颖 纠正数据采集的方法，以及3）在现场和虚拟培训课程中运行。这 异质性核心是我们SD-NSC将创建的研究资源的关键组成部分。 该核心的价值是由年龄等效诱导的细胞类型和类器官的增强的。 衰老核心的人体细胞模型以及衰老综合模型中的新型机器学习能力 核。我们将共同为衰老领域基本生物学的研究人员提供必要的资源 将关键的发现纳入我们年龄的机制。异质性核心将使研究能够 衰老的细胞细胞和组织异质性以及最终的贡献和机制 异质性导致衰老的变性和功能障碍。