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

生物样本核心-项目总结 衰老细胞在发育和疾病中发挥作用。因为衰老的累积 刺激随着时间增加，衰老细胞在衰老组织中积累。虽然衰老细胞可能 保护，他们也可以燃料老化和病理条件，通过基因表达的变化和收购 衰老相关分泌表型（SASP）SASP包括细胞因子分泌的改变， 趋化因子、生长因子和蛋白酶，它们可引起慢性无菌性炎症并改变周围环境。 组织结构和功能。我们的组织绘图中心的首要目标，通过协调努力， 管理、生物标本、生物分析和数据分析核心，将产生一个蓝图， 在单细胞分辨率下使用形态学、蛋白质组学和转录组学方法研究细胞衰老 三种健康的人体组织：卵巢、乳房和骨骼肌。SASP将在卵泡中接受询问 通过先进的蛋白质组学，研究卵巢生物液。此外，我们将评估系统性 匹配的尿液和血浆样本中的SASP。为此，生物样本核心将与西北大学合作 大学、科门组织库和维克森林大学进行回顾性和前瞻性收集 通过IRB从知情同意的成人中获得的组织、匹配的液体以及相关的人口统计学和临床数据- 批准的方案和程序。样本将包括：卵巢组织（N=50，42- 78岁）、卵泡液（N=50， 27- 45岁）、乳腺活检（N=66，29- 66岁）和骨骼肌活检（N=88，年轻人（20- 30岁）和 老年人（> 70岁）。重要的是，股外侧肌（VL）肌肉活检将间隔3年纵向收集 来自健康男性和女性，D3肌酸尿测量将用于将细胞 与全身肌肉质量相关的衰老特征。生物样本核心将采购，策划，验证， 将组织分发给生物分析中心和其他SenNet组织图谱中心。映射衰老 卵巢、乳腺和肌肉中的细胞将首次揭示 生殖和体细胞组织，并将阐明无处不在的和组织特异性签名的细胞 衰老此外，这三个组织与衰老有关，因为：1）卵巢在人类中首先老化 2）乳房表现出强烈的SASP， 老化并具有高脂肪含量，其通常表现出细胞衰老，以及3）骨骼肌退化 与肌肉减少症有关，肌肉减少症是与年龄有关的虚弱的最常见原因，股外侧肌是其中之一 影响体能的第一个组织。肌肉活检将纵向获得， 重复活检之间的间隔是人类衰老分子研究中最长的尝试， 男性和女性的肌肉。因此，我们能够很好地揭示细胞衰老的负担， 以前所未有的方式生活。

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.