Cellular senescence is a hallmark of aging and is increasingly linked to a variety of age-related diseases. However, our understanding of senescence in human tissues is extremely limited. To begin to address these significant knowledge gaps, the TriState SenNet Tissue Mapping Center (TMC) will analyze human lung and heart tissue to provide a high-resolution map of the senescent cell population in these organs. With the combined expertise of the University of Pittsburgh, Carnegie Mellon University, Ohio State University, and the University of Rochester School of Medicine, this consortium will provide a comprehensive assessment of two organs linked to a variety of age-related diseases. Our analysis will be multi-modal and include high-content, unbiased approaches involving single cell RNA/ATAC sequencing, proteomics, and spatial transcriptomics. In addition, as part of our mapping endeavor, the TriState SenNet TMC will analyze the relationship between the initiating trigger for senescence and the subsequent senescent cell phenotype using precision-cut tissue sections from human lungs and hearts. We will also purify and isolate senescent and non-senescent cells from an individual donor lung and use these isogenic primary cells to deconvolute the physiologically relevant driver of human senescence. Together, this combined analysis of tissue and tissue slices/cells from the same individual will provide an unrivaled, unprecedented, in-depth, high-resolution map of the senescent cell population in the human lung and heart, define the physiological drivers of senescence, and provide a rational approach to understand the therapeutic potential of senolytic therapy.

Overall approach of the TriState SenNet TMC and interaction of the Biological Analysis, Biospecimen, and Data Analysis Cores