Core 1: Human Cell Models of Aging Core

项目摘要-衰老核心的人体细胞模型 SD-NSC衰老核心(人类细胞核心)人体细胞模型致力于建立新的细胞模型 来自人类成纤维细胞的衰老，包括来自代表整个成人广度的独特队列的成纤维细胞 按时间顺序计算年龄，并对生物年龄的生理和功能测量进行注释。遗传模型 长期以来，生物体对衰老研究一直很重要，但动物在多大程度上 模型忠实地代表了人类衰老的分子和细胞过程。这件事的首要目标是 核心是创建强大的新的基于人类细胞的模型，使对分子的广泛研究成为可能 以及人类衰老的细胞异质性。生成这些新的人体衰老模型的方法 主要来源于通过直接转化皮肤细胞样本来创造诱导细胞类型的最新进展。 人类细胞核心联合负责人盖奇博士的开创性工作表明，衰老的特征是 维持在这些诱导细胞类型中。将这种方法与同样新的创建3D的方法相结合 代表不同器官和组织微环境的有机细胞培养，能够创造 史无前例的基于人体细胞的组织衰老模型。这些模型将实现对细胞的可靠分析 人类衰老过程中的异质性。作为这项努力的一部分，核心将招募范围广泛的人类对象 年龄从20岁到70岁以上，从而代表了健康成年人年龄跨度的全部。这些 参与者将就生物衰老的关键临床和生理特征进行广泛的表型分析，以及 将采集血液和皮肤样本。皮肤样本将用于提取原代真皮成纤维细胞，来自 其中包括重新编程的干细胞和直接诱导的细胞类型，并将被创建和存储以供共享。 人类细胞核心将为直接诱导不同类型的细胞和创造 器官类，包括胰腺、肾脏、肝脏、心脏、平滑肌和血管系统。以促进吸纳 在整个老龄化基础生物学研究社区的这些新的人类细胞模型中，Core将提供 与研究开发核心一起举办讲习班和培训班。协议，特定 试剂，细胞将直接从人类细胞核心分发到NSC附属机构，更广泛地 通过开放资源和细胞库，如科里尔研究所的NIA衰老细胞库和 阿德金。受试者的表型数据将与细胞系一起共享。重要的是，人类细胞的核心是 设计为与SD-NSC的其他研究资源核心集成，作为人类细胞模型 (具有特定主题的数据)可以直接输入到老化核心的异构性中，以进行系统级分析 老化过程(多组学和高级成像)。然后，可以将这些复杂的数据集输入到 用于新的和现有的综合分析的老化核心的综合模型。人类细胞 核心，作为独立的资源，作为SD-NSC核心管道的集成组件，将创建 为研究细胞异质性在人类衰老过程中的影响提供了新的机会。

PROJECT SUMMARY – Human Cell Models of Aging Core The SD-NSC Human Cell Models of Aging Core (Human Cell Core) is focused on creating new cellular models of aging from human fibroblasts, including fibroblasts from a unique cohort representing the full breadth of adult chronological age and annotated for physical and functional measures of biological age. Genetic model organisms have long been important for aging research, but there are limitations to the extent to which animal models faithfully represent the molecular and cellular process of human aging. The overarching goal of this Core is to create powerful new human cell-based models to enable a wide range of studies into the molecular and cellular heterogeneities of human aging. Approaches for generating these new human models of aging draw largely from recent advances in creating induced cell types via the direct conversion of skin cell samples. Pioneering work from the Human Cell Core co-Lead, Dr. Gage, has shown that aging characteristics are maintained in these induced cell types. Pairing this approach with equally new approaches for creating 3D organoid cell cultures representative of different organ and tissue microenvironments, enables the creation of unprecedented human cell-based models of tissue aging. These models will enable robust analyses of cellular heterogeneities in human aging processes. As part of this effort, the Core will recruit human subjects ranging in age from 20–70+ years, thereby representing the full breadth of the healthy adult human age span. These participants will be extensively phenotyped for key clinical and physiological features of biological aging, and blood and skin samples will be collected. Skin samples will be used to derive primary dermal fibroblasts, from which both reprogrammed stem cells and directly induced cell types will be created and banked for sharing. The Human Cell Core will develop protocols for the direct inducement of different cell types and for the creation of organoids, including pancreas, kidney, liver, heart, smooth muscle, and vasculature. To promote the uptake of these new human cell models throughout the basic biology of aging research community, the Core will offer workshops and training sessions in conjunction with the Research Development Core. The protocols, specific reagents, and cells will be distributed to NSC affiliates directly from the Human Cell Core, and more broadly through open resources and cell repositories like the NIA Aging Cell Repository at the Coriell Institute and Addgene. Subject phenotype data will be shared along with the cell lines. Importantly, the Human Cell Core is designed to be integrated with the other Research Resource Cores of the SD-NSC, as human cell models (with subject-specific data) can be fed directly into the Heterogeneity of Aging Core for systems-level analysis of aging processes (multi-omic and advanced imaging). These complex datasets can then be fed into the Integrative Models of Aging Core for the application of new and existing integrative analyses. The Human Cell Core, as a stand-alone resource, and as an integrated component of the SD-NSC Core pipeline, will create substantial new opportunities to investigate the influences of cellular heterogeneity in human aging processes.