Biospecimen Core for Procurement of Human Somatic and Reproductive Tissues for Senescent Cell Mapping

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BIOSPECIMEN CORE - PROJECT SUMMARY Senescent cells play a role in development and disease. Because the cumulative exposure to senescence stimuli increases with time, senescent cells accumulate in aging tissues. Although senescent cells may be protective, they can also fuel aging and pathologic conditions through gene expression changes and acquisition of a Senescence Associated Secretory Phenotype (SASP). The SASP consists of altered secretion of cytokines, chemokines, growth factors, and proteases, which can cause chronic sterile inflammation and alter surrounding tissue structure and function. The overarching goal of our Tissue Mapping Center, via the coordinated efforts of the Administrative, Biospecimen, Biological Analysis, and Data Analysis Cores, is to generate a blueprint of cellular senescence using morphometric, proteomic and transcriptomic approaches at single cell resolution in three healthy human tissues: the ovary, breast, and skeletal muscle. The SASP will be interrogated in follicular fluid, the associated ovarian biofluid, through advanced proteomics. Moreover, we will evaluate the systemic SASP in matched urine and plasma samples. To this end, the Biospecimen Core will partner with Northwestern University, the Komen Tissue Bank, and Wake Forest University for the retrospective and prospective collection of tissues, matched fluids, and associated demographic and clinical data from consenting adults via IRB- approved protocols and procedures. Samples will include: ovarian tissue (N=50, 42-78y), follicular fluid (N=50, 27-45y), breast biopsies (N=66, 29-66y), and skeletal muscle biopsies (N=88, balanced for young (20-30y) and old (>70y) ages). Importantly, vastus lateralis (VL) muscle biopsies will be collected longitudinally 3 years apart from healthy males and females, and D3 creatine urine measurements will be used to correlate cellular senescence signatures with total body muscle mass. The Biospecimen Core will procure, curate, validate, and distribute tissues to the Biological Analysis Core and other SenNet Tissue Mapping Centers. Mapping senescent cells in ovary, breast, and muscle will provide the first insights into cellular senescence differences between reproductive and somatic tissues and will elucidate ubiquitous and tissue-specific signatures of cellular senescence. Moreover, these three tissues are relevant to aging because: 1) the ovary ages first in the human body and is associated with a fibro-inflammatory microenvironment, 2) the breast exhibits a strong SASP with aging and has a high fat content which often exhibits cellular senescence, and 3) skeletal muscle deterioration is associated with sarcopenia, the most common cause of age-related frailty, with the vastus lateralis being one of the first tissues affecting physical performance. The muscle biopsies will be obtained longitudinally, with the interval between repeated biopsies being the longest yet attempted in molecular studies on human aging in muscle in both sexes. Thus, we are well positioned to reveal the burden of cellular senescence across the lifespan in an unprecedented manner.