San Diego Nathan Shock Center

摘要 虽然衰老的特征是进行性的、全身性的、生理性的和细胞性的衰退，但衰老的程度是由衰老引起的。 这些发生是高度异质性的，特别是在老年人中。这一补充的目的是圣 迭戈内森休克中心（SD-NSC）是创造新的机会，为老龄化研究社区的研究 人类衰老的异质性SD-NSC提供新的工具、资源和培训机会， 使研究人类衰老的异质性成为可能。这些活动的核心是人类细胞模型， 目前正在招募一个新的人类临床队列（SD-NSC-CC），代表成年人 生命历程（20-85岁以上）。我们建议加强SD-NSC-CC，招收来自以下地区的老年人参加 Rancho Bernardo研究（RBS）是NIH最长的基于人群的观察队列之一，包括 纵向临床评估。到目前为止，RBS的参与者已经接受了多达七次的身体和认知测试。 评估超过28年，使我们能够招募代表不同健康轨迹的RBS参与者， 衰老该补充的具体目的是：1）提供生物样品和数据资源， 研究人员确定年龄依赖的健康轨迹如何与异质性老龄化相关，2）促进 开发与RBS纵向数据相关的新型人类衰老细胞模型，以及3） 利用现有的SD-NSC基础设施，向老龄化研究宣传这些新资源的可用性 社区.我们将共同入组SD-NSC-CC，40名RBS受试者（≥ 65岁），代表一个范围 长期老化轨迹（即生物学年龄），包括对长期物理 和认知能力下降将收集成纤维细胞、血浆/血清和血细胞并储存， 提供给衰老生物学研究界。衰老核心的人类细胞模型还产生了 iPSC和其它诱导的细胞类型（例如，神经元）从成纤维细胞，维持细胞老化的特点， 供体通过将具有已知认知和身体功能轨迹的RBS患者纳入该管道，我们将 显著增加SD-NSC生成的细胞模型库，从而增加 苏格兰皇家银行和SD-NSC的研究社区。目前的SD-NSC-CC认知电池也将在 扩展以匹配RBS认知评估，从而能够收集新的纵向认知数据。 最后，SD-NSC提供试点资金，以支持老龄化研究项目的异质性， 这将扩大到包括那些使用这些新资源的人。综上所述，这种补充将成倍增加 SD-NSC和RBS的价值，并增加衰老生物学研究所需的资源 了解人类衰老的异质性。

ABSTRACT While aging is characterized by progressive, systemic, physiological, and cellular declines, the degree to which these occur is highly heterogeneous, particularly among older adults. The goal of this supplement to the San Diego Nathan Shock Center (SD-NSC) is to create new opportunities for the aging research community study the heterogeneity of human aging. The SD-NSC generates novel tools, resources, and training opportunities to enable studies into the heterogeneity of human aging. Central to these activities is the Human Cell Models of Aging Core that is currently enrolling a new human clinical cohort (the SD-NSC-CC) representative of the adult lifecourse (20-85+ years old). We propose to enhance the SD-NSC-CC by enrolling older adult participants from the Rancho Bernardo Study (RBS), one of NIH’s longest population-based observational cohorts that includes longitudinal clinical assessments. To date, RBS participants have undergone up to seven physical and cognitive assessments over 28 years, allowing us to enroll RBS participants representing different trajectories of healthy aging. The specific aims of this supplement are: 1) to provide biological samples and data resources to enable researchers to determine how age-dependent health trajectories relate to the heterogeneity aging, 2) to facilitate the development of novel human cell models of aging that are linked to longitudinal data from the RBS, and 3) to utilize existing SD-NSC infrastructure to advertise the availability of these new resources to the aging research communities. We will co-enroll into the SD-NSC-CC, 40 RBS participants (≥ 65 years old) representing a range of long-term aging trajectories (i.e. biological ages), including resilience and susceptibility to long term physical and cognitive decline. Fibroblasts, plasma/serum, and blood cells will be collected and banked and made available to the biology of aging research community. The Human Cell Models of Aging Core also generates iPSCs and other induced cell types (e.g., neurons) from fibroblasts that maintain cellular aging features of the donor. By including RBS patients with known cognitive and physical function trajectories in this pipeline, we will significantly augment the library of cell models being generated by the SD-NSC, thus increasing the impact of both the RBS and SD-NSC for the research community. The current SD-NSC-CC cognitive battery will also be expanded to match RBS cognitive assessments, to enable the collection of new longitudinal cognitive data. Finally, the SD-NSC provides pilot funding to support heterogeneity of aging research projects, the scope of which will be expanded to include those using these new resources. In summary, this supplement will multiply the value of both the SD-NSC and the RBS and enhance the resources needed by the biology of aging research community to understand the heterogeneity of human aging.