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.

项目概要——总体 由于衰老是大多数人类疾病和个体整体功能衰退的最大危险因素， 人们对了解其生物学基础非常感兴趣，最终目标是增加 人类生命中健康且富有生产力的年数（即健康寿命）。保守的衰老机制和 通过对衰老的基本生物学的研究，人们已经确定了长寿。这些包括模型研究 这些生物体也表明衰老具有柔韧性，为促进健康寿命的干预措施打开了大门。 然而，阻碍我们理解衰老和干预能力的一个主要复杂因素是 过程的内在异质性和诱导异质性。不同的细胞类型具有本质上不同的衰老过程 模式，甚至相同的细胞类型也会以不同的速度老化，具体取决于生理环境或 环境暴露。这些和其他细胞异质性（例如，改变的表观遗传状态和基因 表达）可以驱动组织功能障碍和与年龄相关的病理，最终影响健康寿命和 寿命。通过实验揭示这种复杂性需要应用强大的单细胞和成像技术 正面解决细胞衰老异质性的方法，以及计算和数学 阐明衰老网络和通路相互作用的建模方法，涉及已知的特征 老化。衰老研究的另一个主要差距是需要新的、更好的人体细胞和组织模型 允许与人类衰老直接相关的基础研究。因此，拟议的 San 迭戈·内森休克中心 (SD-NSC) 旨在创建必要的基础设施，以促进和促进 系统研究衰老过程中的细胞异质性，为基础人类提供新的细胞和组织模型 衰老研究。 SD-NSC 将建立尖端研究资源核心，重点关注：1）新型人类 衰老的细胞和类器官模型，包括来自独特的人类衰老队列的物理注释 和生物年龄的功能测量，2）单细胞和高分辨率组学和成像技术， 3）老化网络的计算建模。 SD-NSC 研究资源核心将提供 为国家安全委员会网络和老龄化研究界提供科学服务，并传播样本、数据集 协议和计算工具。这些资源将得到研究开发核心的补充 中心外展活动将提供：1) 试点资助和定制指导计划 鼓励和支持早期和成熟的研究人员新进入老龄化研究，2）创新的in- 解决细胞异质性的先进方法和技术的人员和虚拟培训，以及 3) 通过新颖的编程来鼓励协作和传播知识领导力 与衰老的基础生物学相关的知识。 SD-NSC 将汇集互补的专业知识和 来自圣地亚哥三个著名研究机构的资源，其共同目标是了解 细胞异质性在衰老中的作用，最终使干预措施能够延长人类的健康寿命。