Core 2: Heterogeneity of Aging

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PROJECT SUMMARY – Heterogeneity of Aging Core In line with the pioneering work of Nathan Shock, it is clear that aged tissues accumulate cellular heterogeneity or mosaicism. This heterogeneity is likely a cause of aging due to impairments in both intercellular interactions and the coordination of tissue function. The Heterogeneity of Aging Core (Heterogeneity Core) within the San Diego Nathan Shock Center of Excellence in Basic Biology of Aging (SD-NSC) will enable investigators to probe the heterogeneity of aging over a broad range of scales (from molecules to organelles to single cells and tissues) by providing access to a diverse suite of state-of-the-art instrumentation and analytical technologies, as well as experienced Core staff. The Core will provide specific resources for studying key processes implicated in aging and disease at high resolution, including single-cell next-generation sequencing platforms, high-resolution imaging systems, and mass spectrometry approaches to measure proteomic and metabolomics signatures of aging in cells and tissues, with an emphasis on cell-cell heterogeneity and heterogeneity across tissues. These technologies are rapidly evolving and will continue to do so over the coming years. Utilizing established Core resources with proven track records for staying current with evolving technologies is the most effective way to ensure new innovations in analytical technologies are available to the greatest breadth of aging researchers. The Heterogeneity Core provides specific support for researchers in the aging field by: 1) providing access to specific scientific services, advice, and expertise, 2) developing and disseminating novel methods for correlative data acquisitions, and 3) running on-site and virtual training sessions. The Heterogeneity Core is a critical component in the pipeline of research resources that our SD-NSC will create. The value of this Core is bolstered by the generation of age-equivalent induced cell types and organoids by the Human Cell Models of Aging Core, and novel machine-learning capabilities in the Integrative Models of Aging Core. Together we will provide researchers in the basic biology of aging field with the resources necessary to make key discoveries into the mechanisms by which we age. The Heterogeneity Core will enable studies into the cell-cell and tissue heterogeneity of aging and, ultimately, the contributions and mechanisms by which heterogeneity causes the degeneration and dysfunction that characterizes aging.