San Diego Nathan Shock Center

圣地亚哥内森休克中心

• 批准号: 10045533
• 负责人: GERALD SHADEL
• 金额: $ 103.21万
• 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/10045533
• 关键词: Address; Advocate; Age; Aging; Anatomy; Animal Model; Artificial Intelligence; Basic Science; Biological; Biological Aging; Biological Markers; Biological Models; Biology of Aging; Cell Aging; Cell Communication; Cell model; Cells; Chronology; Clinical; Collaborations; Communication; Communities; Complement; Complex; Computer Models; Custom; Data Set; Development; Ensure; Environment; Environmental Exposure; Epigenetic Process; Event; Functional disorder; Gene Expression; Goals; Grant; Head; Heterogeneity; Human; Imaging Techniques; Imaging technology; Individual; Infrastructure; Institution; Intervention; Investigation; Knowledge; Leadership; Life; Location; Longevity; Measures; Mentors; Methods; Mission; Modality; Modeling; Molecular; Organoids; Pathologic; Pathology; Pathway interactions; Persons; Phenotype; Physiological; Pliability; Politics; Process; Protocols documentation; Research; Research Personnel; Resolution; Resources; Risk Factors; Role; Sampling; Services; Shock; System; Technology; Tissue Model; Tissues; Training; age related; career development; cell age; cell type; cellular imaging; cohort; computerized tools; disorder risk; epigenomics; functional decline; healthspan; human disease; human model; human tissue; imaging approach; innovation; interest; intervention effect; mathematical model; meetings; member; multiple omics; new technology; news; novel; outreach; personalized intervention; programs; research and development; single cell analysis; transcriptomics; virtual

PROJECT SUMMARY – Overall Since aging is the biggest risk factor of most human diseases and the overall functional decline in individuals, there is great interest in understanding its biological underpinnings, with the ultimate goal of increasing the number of healthy and productive years of human life (i.e., healthspan). Conserved mechanisms of aging and longevity have been identified via investigations into the basic biology of aging. These include studies in model organisms that have also shown that aging is pliable, opening the door for healthspan-promoting interventions. However, a major complicating factor that impedes our understanding of aging and our ability to intervene is the intrinsic and induced heterogeneity of the process. Distinct cell types have intrinsically different aging modalities, and even identical cell types age at different rates depending on physiological context or environmental exposures. These and other cellular heterogeneities (e.g., altered epigenetic states and gene expression) can drive tissue dysfunction and age-related pathology that ultimately impact healthspan and lifespan. Unravelling this complexity experimentally requires application of robust single-cell and imaging approaches to address the heterogeneity of cellular aging head-on, as well as computational and mathematical modelling approaches to illuminate aging networks and pathway interactions that involve known hallmarks of aging. Another major gap in aging research is the need for new and better human cell and tissue models to allow basic research directly relevant to human aging. Thus, the overarching premise of the proposed San Diego Nathan Shock Center (SD-NSC) is to create the requisite infrastructure to facilitate and promote the systematic study of cellular heterogeneity in aging and to provide novel cell and tissue models for basic human aging studies. The SD-NSC will establish cutting-edge Research Resource Cores focused on: 1) novel human cell and organoid models of aging, including from a unique human aging cohort that is annotated for physical and functional measures of biological age, 2) single-cell and high resolution -omics and imaging techniques, and 3) computational modelling of aging networks. The SD-NSC Research Resource Cores will provide scientific services to the NSC Network and the aging research community, and disseminate samples, datasets protocols, and computational tools. These resources will be complemented by a Research Development Core and Center outreach activities that will provide: 1) pilot grants and customized mentoring programs to encourage and support early-stage and established investigators new to aging research, 2) innovative in- person and virtual training in advanced methods and technologies to address cellular heterogeneity, and 3) intellectual leadership through novel programming to encourage collaboration and the dissemination of knowledge related to the basic biology of aging. The SD-NSC will bring together complementary expertise and resources from three renowned San Diego research Institutions with the common goal of understanding the role of cellular heterogeneity in aging to ultimately enable interventions to extend human healthspan.

项目摘要 - 总体 由于衰老是大多数人类疾病的最大危险因素，并且个人的总体功能下降，因此 人们对了解其生物学基础有极大的兴趣，其最终目标是增加 人类生活的健康和生产力的数量（即健康范围）。保守的衰老机制 通过研究衰老的基本生物学，已经确定了寿命。这些包括模型中的研究 还表明衰老很柔软的生物为促进HealthSpan的干预措施打开了大门。 但是，阻碍我们对衰老的理解和干预能力的主要复杂因素是 该过程的固有和诱导的异质性。不同的细胞类型具有本质上不同的衰老 模态，甚至相同的单元类型以不同的速度年龄，具体取决于物理上下文或 环境暴露。这些和其他细胞异质性（例如，表观遗传状态和基因改变 表达）可以驱动组织功能障碍和与年龄相关的病理学，最终影响健康范围和 寿命。在实验上阐明这种复杂性需要应用鲁棒的单细胞和成像 解决细胞衰老的异质性的方法，以及计算和数学 启动衰老网络和途径相互作用的建模方法，涉及已知标志 老化。衰老研究的另一个主要差距是需要新的，更好的人类细胞和组织模型才能 允许基础研究与人类衰老直接相关。那是拟议的SAN的总体前提 迭戈·内森（Nathan）冲击中心（SD-NSC）是创建必要的基础设施，以促进和促进 衰老中细胞异质性的系统研究，并为基本人类提供新颖的细胞和组织模型 aging studies. SD-NSC将建立尖端的研究资源核心：1）新型人类 衰老的细胞和器官模型，包括从独特的人衰老队列中进行注释 生物年龄的功能度量，2）单细胞和高分辨率 - 组和成像技术， 3）老化网络的计算建模。 SD-NSC研究资源核心将提供 NSC网络和老化研究社区的科学服务，并传播样本，数据集 协议和计算工具。这些资源将由研究开发核心完成 以及将提供的中心外展活动：1）试点赠款和定制的心理计划 鼓励和支持早期研究的早期研究人员，刚开始老化研究的研究人员，2） 高级方法和技术的人和虚拟培训以解决细胞异质性，3） 通过新颖的编程进行智力领导，以鼓励合作和传播 与衰老的基本生物学有关的知识。 SD-NSC将汇集完整的专业知识和 来自三个著名圣地亚哥研究机构的资源，其共同目标是了解 细胞异质性在衰老中的作用，最终使干预措施扩展人类健康状况。