The overall goal of the JHU-Mayo-NIA Murine Senescence Mapping Program (JMN-MSMP) is to create an Atlas of Senescence in Murine Tissues across the lifespan. The proposal encompasses unique and novel biological and computational resources and strategies to map senescent cells (SnCs) in murine tissues. Biological resources include aging mouse colonies of multiple strains, including those with reporters for identification of SnCs. We also have access to a robust murine tissue bank and cataloging infrastructure for aging tissues, including those with age-related pathology. Computational resources include single-cell sequencing and spatial transcriptomics expertise, transfer learning algorithms that can identify SnCs and elucidate cell communication from single-cell datasets, and integration of genomics and multiple imaging modalities to identify SnCs in tissues in 2D and 3D. For this proposal, the JMN-MSMP team will focus first on developing a timeline of the emergence of senescence markers in plasma/serum in tissues from the National Institute of Aging murine aging program including brain. Importantly, we have archived tissues from two genetically distinct strains of laboratory mice of both sexes over their lifespan that will allow us to implement a rigorous and multidimensional analysis as soon as the Program is funded. This will be followed by in depth single cell analysis of selected tissues for senescence mapping. The JMN-MSMP will consist of three Core components: the Administrative Core (AC), Biological Analysis Core (BAC), and Data Analysis Core (DAC). The Specific Aims of the JMN-MSMP are: Aim 1. Overall JMN-MSMP Research Strategy: Integrate genomics and imaging strategies to build a comprehensive Atlas of Senescence in Murine Tissues, and to define the physiological impact of senescent cells. Aim 2. Overall JMN-MSMP Management Strategy, Goals, and Milestones: Provide infrastructure to support an integrated research effort toward creation of the Atlas. Aim 3. JMN-MSMP Resource Sharing: Ensure that tissues, data, methods, and technologies are available to other TMCs, and that appropriate data deposition and sharing policies are in place.