PROJECT SUMMARY/ABSTRACT BIOLOGICAL ANALYSIS CORE The primary objective of the Biological Analysis Core (BAC) of the JAX-Sen mouse Tissue Mapping Center (TMC) is to provide high resolution state-of-the-art molecular, cellular, and tissue-level characterization of mouse tissues for the purpose of identifying robust biomarkers of senescence and, from this, build tissue- specific atlases at the cellular, microenvironment, and secretome levels. The BAC will generate high resolution, high content, high-throughput biomolecular data to generate comprehensive maps of cellular senescence in six primary mouse tissues, across two mouse model systems - a large cohort of Diversity Outbred (DO) mice representing genetic diversity and the required C57BL/6 strain. To achieve these goals, the BAC will 1) develop and apply a pipeline to generate unbiased, high-quality, high-resolution, and high-throughput datasets to discover biomarkers of senescence, 2) develop a high-throughput, high-content tissue phenotyping pipeline and apply this to a cohort of 400 DO mice, 3) generate high biomolecular content, multi-parameter spatial measurements on 2D serial sections to enable 3D tissue reconstruction, and 4) leverage p16/p21 reporter mouse lines to comprehensively profile senescent cells sorted from aged mice. Once complete, this project will have generated multi-scale, multi-dimensional maps of senescence cells within six mouse tissues from control and senolytics treated tissues, information that will be critical to optimize and guide future senolytic interventions in human trials.