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.

抽象的老年人容易经历肌肉废用期，导致肌肉萎缩和无力。此外，老年人废用事件后的肌肉恢复也会受到损害。因此，高度优先考虑面对快速增长的人口老龄化，需要进一步了解背后的细胞机制随着年龄的增长肌肉再生受损。巨噬细胞和其他免疫细胞群（例如 T 细胞）在停用一段时间后，最佳地恢复肌肉大小至关重要，然而，在这种情况下，它们的作用令人惊讶的是，骨骼肌老化的情况尚未得到阐明。因此，使用成熟的肌肉废用和再生的小鼠模型，我们已经制作了令人信服的初步数据，证明老年小鼠肌肉再生受损，并伴有巨噬细胞免疫反应改变以及恢复期间骨骼肌的募集。在当前的提案中，我们建议开展一次年老和年轻小鼠肌肉巨噬细胞（和其他免疫细胞）反应的长时间过程从停用恢复期间。我们还将确定抑制幼鼠巨噬细胞的募集是否会导致老年小鼠从废弃状态恢复期间的表型特征。我们将利用组合独特的 FACS 和单细胞 RNA 测序的方法可以广泛解决这些问题。这些数据将为调查巨噬细胞和其他上游介质的其他机制研究奠定基础从废弃状态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老肌肉的恢复。