San Diego Nathan Shock Center

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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.