Biospecimen-Core

Project Summary Senescent cells (SnCs) accumulate with age and in various chronic disease states and clearly contribute to driving morbidity and mortality in model organisms. Drugs that selectively eliminate SnCs (“senolytics”) were first developed by our team and have been demonstrated to reduce frailty, extend median lifespan, and attenuate morbidity in murine models of numerous age-related diseases. However, SnCs also play a role in wound healing and tissue remodeling. To advance senolytics to their greatest potential, then, it is imperative to understand more about SnCs in humans with healthy aging. As part of SenNet, the proposed Minnesota Tissue Mapping Center (MN TMC) has selected four tissues for identification, characterization, and spatio-temporal analysis of senescence: adipose, skeletal muscle, liver, and ovarian tissues. These tissues were selected because of the scientific expertise at UMN and Mayo Clinic in the biology of these organs, evidence of increased senescence with age, and availability of biobanked specimens as well as surgical access to fresh tissues from healthy individuals. The overall goal of the Biospecimen Core (BSP), co-directed by Dr. Sayeed Ikramuddin, Chair of the UMN Department of Surgery, and Dr. Oyedele Adeyi, Professor of Laboratory Medicine and Pathology, is to provide the tissues and blood for PBMC isolation to the Biological Analysis Core (BAC) for bulk, single cell, and spatial analysis of human SnCs for subsequent multi-plex analysis of the results by the Data Analysis Core (DAC). The BSP will leverage their strong track record of obtaining high-quality, well-annotated human samples from non-chronically diseased individuals who are metabolically characterized and with appropriate diversity in gender, race, socio-economic status, ethnicity, and other relevant diversity parameters. The BSP will also provide access to UMN’s specimen procurement network (BioNet) that has ~70,000 archival tissues (frozen, FFPE) and biofluids (frozen) collected for research, including several adipose depots, several muscles, liver from organ donors, and healthy ovarian tissues removed because of benign lesions. In addition, the BSP has access to tissues within the Rochester Epidemiology Project, which encompasses the medical records of all citizens living in Olmsted County, MN since 1966, along with archived biological specimens. The Aims of the BSP are to: 1) Prepare and maintain all regulatory materials supporting human tissue collection; 2) Recruit and consent patients of different ages for this project; 3) Characterize the metabolic health of enrolled participants; 4) Coordinate with BioNet for intraoperative specimen collection, annotation, and storage of tissues; 5) Procure and annotate high quality target tissues along with relevant biofluids; 6) Longitudinally follow patients for which weight loss and bariatric surgery are metabolic perturbations; 7) Disseminate the samples to MN TMC BAC; and 8) Partner with SenNet to share tissues and to develop shared patient consent and tissue collection protocols with appropriate Ethical, Legal and Social Implications and quality control and assurance considerations.