Role of immune cells on the growth and recovery of aging muscle

免疫细胞对衰老肌肉生长和恢复的作用

基本信息

批准号：
10197500
负责人：
Micah J Drummond
金额：
$ 5.78万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-03-15 至 2022-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10197500
关键词：
Address Adult Aging Anti-Inflammatory Agents Attenuated Automobile Driving Blood Bone Marrow CCL2 gene Cell physiology Cells Characteristics Complex Data Development Disuse Atrophy Elderly Event Expression Profiling Flow Cytometry Foundations Functional disorder Future Gene Expression Gene Expression Profile Genetic Genomics Growth Health Immune Immune response Immunotherapy Impairment Inflammatory Injury Knockout Mice Lead Ligands Mediator of activation protein Messenger RNA Methodology MicroRNAs Mus Muscle Muscle Cells Muscle Weakness Muscular Atrophy Phenotype Play Population Positioning Attribute Process Recovery Recovery of Function Regulatory T-Lymphocyte Risk Role Skeletal Muscle T-Lymphocyte Testing Time Tissues Treatment Efficacy age related aged aging population angiogenesis cell type chemokine design disability experience fall risk falls fibrogenesis injured injury recovery insight macrophage monocyte mouse model muscle aging muscle strength neutrophil novel physical inactivity prevent reconstitution recruit response single-cell RNA sequencing skeletal muscle wasting transcriptome

项目摘要

Abstract Older adults are prone to experience periods of muscle disuse resulting in muscle atrophy and weakness. Moreover, muscle recovery following a disuse event is impaired in older adults. Therefore, a high priority in the face of a rapidly growing aging population is a need to further understand the cellular mechanisms behind impaired muscle regrowth with aging. Macrophages and other immune cell populations (e.g., T-cells) are of critical importance to optimally restore muscle size following a period of disuse, however, their role under such conditions in aging skeletal muscle has surprisingly not been elucidated. Therefore, using a well-established mouse model of muscle disuse and regrowth, we have produced compelling preliminary data demonstrating impaired muscle regrowth in aged mice and this is accompanied by an altered macrophage immune response and recruitment in skeletal muscle during recovery. In the current proposal, we have proposed to conduct an extensive time course of the muscle macrophage (and other immune cells) response in old and young mice during recovery from disuse. We will also determine if inhibiting macrophage recruitment in young mice will result in a phenotype characteristic of old mice during recovery from disuse. We will utilize combined unique approaches of FACS and single cell RNA sequencing to extensively address these questions. These data will be foundational for additional mechanistic studies investigating upstream mediators of macrophage and other immune cell responses during recovery from disuse while also using novel immunotherapies to optimize muscle recovery in older muscle.

抽象的老年人很容易体验肌肉消失的时期，导致肌肉萎缩和无力。此外，老年人的肌肉恢复会受到损害。因此，高度重视面对迅速增长的衰老人群的面临是需要进一步了解背后的细胞机制随着衰老而造成的肌肉再生。巨噬细胞和其他免疫细胞种群（例如，T细胞）为但是，在一段时间后，对最佳恢复肌肉大小的重要性至关重要，但是，它们在这种情况下的作用衰老骨骼肌的状况尚未阐明。因此，使用良好的肌肉废除和再生的小鼠模型，我们产生了引人入胜的初步数据老年小鼠的肌肉再生受损，这伴随着巨噬细胞免疫反应改变并在恢复过程中招募骨骼肌。在当前的提案中，我们提议进行肌肉巨噬细胞（和其他免疫细胞）反应的大量时间过程在恢复废弃期间。我们还将确定抑制年轻小鼠的巨噬细胞募集是否会导致在恢复废弃过程中旧小鼠的表型中。我们将利用合并的独特 FACS和单细胞RNA测序的方法可以广泛解决这些问题。这些数据将为研究巨噬细胞和其他其他机械研究的基础在失业中恢复期间的免疫细胞反应，同时还使用新型免疫疗法来优化肌肉恢复较老的肌肉。