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Targeting macrophage polarization to optimize muscle regrowth from disuse atrophy

靶向巨噬细胞极化以优化废用性萎缩的肌肉再生

基本信息

批准号：
10228828
负责人：
Micah J Drummond
金额：
$ 63.43万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-15 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10228828
关键词：
Acute Address Adopted Aerobic Exercise Age Aging Anti-Inflammatory Agents Area Attenuated Bone Marrow Bone Marrow Cells Bone Marrow Transplantation Cell physiology Cells Chronic Coupled Data Defect Development Disuse Atrophy Effectiveness Elderly Event Fibrosis Foundations Fracture Functional disorder Genomics Growth Factor Health Hematopoietic Hindlimb Hindlimb Suspension Human IGF1 gene Immune Immune system Immunofluorescence Immunologic Immunotherapy Impairment Individual Injury Intramuscular Intramuscular Injections Lead Macrophage Colony-Stimulating Factor Metabolic Diseases Methodology Mus Muscle Muscle function Operative Surgical Procedures Phenotype Population Publishing Recovery Recovery of Function Resolution Running Series Signal Transduction Skeletal Muscle Testing Therapeutic Time Toxin Transplantation age related aged aging population base bone bone aging cytokine disability evidence base experimental study fall risk falls immunoregulation improved loss of function macrophage monocyte mouse genetics mouse model muscle aging muscle regeneration novel pre-clinical prevent recruit repaired response restoration sarcopenia single-cell RNA sequencing

项目摘要

Abstract Muscle recovery following a disuse event is impaired in many older adults which could increase the risk for falls, fractures and disability. We have shown that muscle macrophages are dysregulated during the regrowth period following a disuse event in aged muscle. Therefore, we have proposed a series of elegant, pre-clinical mouse experiments to determine the effectiveness of various immunomodulating therapeutics and identify specific mechanisms underlying age-related muscle immune dysregulation in skeletal muscle during regrowth from disuse. We will utilize state-of-the-art approaches to phenotype muscle macrophages (FACS, single cell RNA sequencing, immunofluorescence) coupled with mouse genetics and bone transfer experiments to extensively address these questions. The data generated will be the first of its kind identifying the mechanisms underlying macrophage dysregulation in aged muscle during regrowth following disuse atrophy while also testing if immunomodulation amplifies muscle and functional recovery in the old.

摘要在许多老年人中，废用事件后的肌肉恢复受损，这可能增加福尔斯的风险，骨折和残疾。我们已经表明，肌肉巨噬细胞在再生期间失调在老化的肌肉中发生废用事件之后。因此，我们提出了一系列优雅的，临床前的小鼠实验以确定各种免疫调节治疗剂的有效性并鉴定特异性免疫调节剂。骨骼肌再生过程中与年龄相关的肌肉免疫失调的潜在机制废弃不用我们将利用最先进的方法来表型肌肉巨噬细胞（流式细胞仪，单细胞RNA 测序，免疫荧光）结合小鼠遗传学和骨转移实验，回答这些问题。所产生的数据将是第一个确定潜在机制的此类数据在废用性萎缩后再生期间，老年肌肉中的巨噬细胞失调，免疫调节增强了老年人的肌肉和功能恢复。