The Jackson Laboratory Senescence Tissue Mapping Center (JAX-Sen TMC)

PROJECT SUMMARY This is a component of a collaborative project within the Cellular Senescence Network (SenNet) Program. We have incorporated known senescence inducers (e.g. Doxorubicin, Palbociclib, high fat diet) in the mouse model and shared relevant tissues (lung, muscle, ovary) with other SenNet TMCs for analysis. In the parent grant to this supplement, we have established The Jackson Laboratory (JAX) Cellular Senescence Network Tissue Mapping Center (JAX-Sen TMC) focused on the analysis of mouse tissue to address a significant research and clinical need for improved biomarkers and cellular maps of senescence. Advances in our understanding of biological aging and the recognition of aging as a modifiable risk factor for many chronic diseases and geriatric syndromes are fueling a growing interest in the cellular underpinnings of the aging process. Despite recent progress in cellular senescence research and the discovery of new senolytics and senomorphics, we lack clear information regarding the role of cellular senescence in aging and age-related disease, and the effect of genetic variation on these phenomena. In the JAX-Sen TMC we are mapping senescent cells in the context of multiple age-matched tissues of genetically defined mouse cohorts, raised in standardized environments throughout their lifespan and defining senescent cell phenotypes associated to features of genetics, age and senolytic interventions. The tissues of specific focus within the JAX-Sen TMC are kidney, pancreas, heart, and placenta. This supplement aims to generate detailed tissue mapping data on the mouse pancreas and kidney derived from our senescence inducers study and perform the analysis of this data using our existing framework. Specifically, we will employ bulk RNA-seq, H&E, CODEX multiplexed antibody imaging, and Xenium in situ RNA spatial profiling. Senescent cells identified from the senescent inducers experiment will be directly compared to those from natural aging, and provide the foundation for future senolytic/senomorphic functional studies.