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

用于获取人体体细胞和生殖组织以进行衰老细胞图谱绘制的生物样本核心

• 批准号: 10376497
• 负责人: Francesca E. Duncan
• 金额: $ 87.87万
• 依托单位: BUCK INSTITUTE FOR RESEARCH ON AGING
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10376497
• 关键词: Biospecimen; Core; Procurement; Human; Somatic

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.

BiospeCimen Core-项目摘要 衰老细胞在发育和疾病中起作用。因为累积暴露于衰老 刺激随时间增加，衰老细胞在衰老组织中积累。尽管衰老细胞可能是 保护性，它们还可以通过基因表达变化和获取来加剧衰老和病理状况 与衰老相关的分泌表型（SASP）的衰老。 SASP包括细胞因子分泌的改变， 趋化因子，生长因子和蛋白酶，可能引起慢性无菌炎症并改变周围 组织结构和功能。我们的组织映射中心的总体目标是通过协调的努力 行政，生物测量，生物分析和数据分析核心是生成蓝图 使用形态计量学，蛋白质组学和转录组方法在单细胞分辨率的细胞衰老 三个健康的人体组织：卵巢，乳房和骨骼肌。 SASP将在卵泡中审问 通过晚期蛋白质组学，流体，相关的卵巢生物裂隙。此外，我们将评估系统性 SASP在匹配的尿液和血浆样品中。为此，BioScecimen Core将与西北地区合作 大学，科门纸巾银行和韦克森林大学，用于回顾性和潜在收集 通过IRB的组织，匹配的流体以及相关的人口统计和临床数据 批准的协议和程序。样品将包括：卵巢组织（n = 50，42-78y），卵泡液（n = 50， 27-45岁），乳房活检（n = 66，29-66y）和骨骼肌活检（n = 88，年轻人平衡（20-30y）和 旧（> 70年）。重要的是，将纵向收集巨大的外侧（VL）肌肉活检 从健康的雄性和女性以及D3肌酸尿液测量中将用于相关 全身肌肉质量的衰老特征。 BiospeCemen Core将采购，策划，验证和 将组织分配到生物分析核心和其他Sennet组织映射中心。映射衰老 卵巢，乳房和肌肉中的细胞将为细胞衰老差异提供第一个见解 生殖和体细胞组织，并将阐明细胞的无处不在和组织特异性特异性 衰老。此外，这三个组织与衰老有关，因为：1）人类的卵巢年龄 身体，与纤维炎性微环境有关，2）乳房表现出强烈的SASP 衰老，脂肪含量高，通常表现出细胞衰老，3）骨骼肌肉恶化 与肌肉减少症是与年龄相关的脆弱原因相关的 最初影响身体表现的组织。肌肉活检将纵向获得 重复活检是人类衰老的分子研究最长但尝试的间隔 性别中的肌肉。因此，我们良好地揭示了整个细胞衰老的负担 寿命以前所未有的方式。