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.

生物样本核心 - 项目摘要 衰老细胞在发育和疾病中发挥作用。因为累积暴露于衰老 随着时间的推移，刺激增加，衰老细胞在衰老组织中积累。尽管衰老细胞可能 它们具有保护作用，还可以通过基因表达的变化和获取来加速衰老和病理状况 衰老相关分泌表型（SASP）的研究。 SASP 由细胞因子分泌的改变组成， 趋化因子、生长因子和蛋白酶，可引起慢性无菌性炎症并改变周围环境 组织结构和功能。我们的组织作图中心的总体目标，通过协调努力 行政、生物样本、生物分析和数据分析核心，是为了生成一个蓝图 使用形态测量、蛋白质组学和转录组学方法以单细胞分辨率研究细胞衰老 三种健康的人体组织：卵巢、乳房和骨骼肌。 SASP 将在卵泡中进行询问 流体，相关的卵巢生物流体，通过先进的蛋白质组学。此外，我们还将评估系统性 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、Komen 组织银行和维克森林大学进行回顾性和前瞻性收集 通过IRB收集来自同意的成年人的组织、匹配的液体以及相关的人口统计和临床数据 批准的协议和程序。样本将包括：卵巢组织（N=50、42-78y）、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，针对年轻人（20-30 岁）和 高龄（>70 岁））。重要的是，股外侧肌 (VL) 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 D3 肌酸尿液测量结果将用于关联细胞 衰老特征与全身肌肉质量。生物样本核心将采购、策划、验证和 将组织分发到生物分析核心和其他 SenNet 组织绘图中心。绘制衰老图 卵巢、乳房和肌肉中的细胞将首次深入了解不同类型细胞之间的细胞衰老差异 生殖和体细胞组织，并将阐明细胞的普遍存在和组织特异性特征 衰老。此外，这三种组织与衰老有关，因为：1）卵巢在人体中最先衰老。 身体并与纤维炎症微环境相关，2）乳房表现出强烈的 SASP 衰老和高脂肪含量通常会表现出细胞衰老，以及3）骨骼肌退化 与肌肉减少症有关，这是与年龄相关的衰弱的最常见原因，股外侧肌就是其中之一 第一个影响身体表现的组织。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迄今为止最长的尝试 男女都有肌肉。因此，我们有能力揭示整个细胞衰老的负担 寿命以前所未有的方式。