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

Biosecimen核心项目摘要 衰老细胞在发育和疾病中发挥作用。因为累积暴露在衰老环境中 刺激随着时间的推移而增加，衰老的细胞在老化的组织中积累。尽管衰老的细胞可能 具有保护性，它们还可以通过基因表达的变化和获得来刺激衰老和病理状况 属于衰老相关分泌表型(SASP)。SASP由细胞因子的分泌改变组成， 趋化因子、生长因子和蛋白水解酶，可引起慢性无菌炎症并改变周围环境 组织结构和功能。我们组织测绘中心的首要目标是通过 管理、生物分析、生物分析和数据分析核心将生成以下蓝图 用形态计量学、蛋白质组学和转录组学方法在单细胞分辨率下研究细胞衰老 三种健康的人体组织：卵巢、乳房和骨骼肌。SASP将在卵泡中被询问 液体，相关的卵巢生物液体，通过先进的蛋白质组学。此外，我们还将评估系统性的 匹配的尿样和血浆样本中的SASP。为此，Biospecimen Core将与西北大学合作 大学、科曼组织银行和维克森林大学进行回顾和预期收集 组织，配对的液体，以及相关的人口统计学和临床数据，通过IRB- 批准的协议和程序。样本包括：卵巢组织(N=50，42-78y)、卵泡液(N=50， 27-45岁)，乳房活检(N=66，29-66岁)和骨骼肌活检(N=88，平衡年轻人(20-30岁)和 高龄(70岁)。重要的是，股外侧肌(VL)的肌肉活检将每隔3年纵向收集一次。 来自健康男性和女性的，以及D3尿肌酸的测量将被用来关联细胞 衰老的标志是全身肌肉质量。Biosecimen Core将采购、管理、验证和 将组织分发到生物分析核心中心和其他Sennet组织测绘中心。地图老化 卵巢、乳房和肌肉中的细胞将提供对细胞衰老差异的第一次洞察 生殖和体细胞组织，并将阐明普遍存在的和组织特有的细胞 衰老。此外，这三种组织与衰老有关，因为：1)卵巢首先衰老。 2)乳房表现出强烈的SASP，与 衰老，脂肪含量高，通常表现为细胞衰老，以及3)骨骼肌退化 与骨质疏松症有关，这是与年龄相关的虚弱的最常见原因，股外侧肌是其中之一。 最早影响身体表现的组织。肌肉活组织检查将纵向进行， 重复活检之间的间隔是迄今为止在人类衰老分子研究中尝试的最长时间 两性都有肌肉。因此，我们处于有利地位，可以揭示世界各地细胞衰老的负担。 以前所未有的方式延长寿命。

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.