PROJECT SUMMARY OVERALL This proposal seeks to establish the KAPP-Sen Tissue Mapping Center Collaborative (TMC) as part of the Cellular Senescence Network: Tissue Mapping Centers effort {RFA-RM-21-008). Our application represents a multidisciplinary collaborative effort involving six leading institutions and aging research programs working together to characterize the distribution and biological heterogeneity of senescent cells in different healthy human tissues in full alignment with the objectives of the Cellular Senescence Network {SenNet). KAPP-Sen brings together skills, resources and perspectives needed to address Sen-Net goals in the framework of the healthy human Kidney. Adipose tissues, Pancreas and Placenta. Given our ability to obtain full thickness skin tissues from individuals providing KAPP samples, we may explore the possibility of future collaborative studies with TMCs selected for their major focus on skin. Our six collaborating institutions located in Farmington. CT (UConn Health, Jackson Laboratory for Genomic Medicine), Boston {Brigham & Women's Hospital, Joslin Diabetes Center), Rochester. MN {Mayo Clinic) and San Antonio. TX {UTHCSA) have all been carefully selected for their essential and unique individual contributions to the field and this effort. Our objectives will be achieved through the following aims: Aim 1 : Coordinate research activities across KAPP-Sen TMC Collaborative sites in support of Sen-Net goals towards mapping cellular senescence and its associated secretory phenotype in the healthy human kidney, adipose tissues, pancreas and placenta. Aim 2: Obtain tissues from healthy kidney transplant donors {kidneys, fat, skin), C-section pregnancies {placenta, cord, fat, skin), outpatient healthy donor biopsies {fat, skin), beating heart brain dead donors {full pancreas) and IIPD/Prodo {dispersed pancreas). Aim 3: Generate highest quality data pertaining to cellular senescence including scRNA-Seq, snRNA-Seq, spatial transcriptomics, immunohistochemistry and Telomere-associated DDR foci {TAFs) in all tissues Aim 4: Perform high level integrative data analysis required for the creation of aUases of human cellular senescence in collaboration with other TMCs, CODDC and NIH staff.

PROJECT NARRATIVE OVERALL We seek to establish the U54 KAPP-Sen Tissue Mapping Center Collaborative with the goal of producing high quality data that would enable SenNet to produce maps of the healthy kidney, adipose tissues, pancreas and placenta across the human lifespan.