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

• 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
• 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

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.

摘要 老年人容易经历肌肉废用期，导致肌肉萎缩和虚弱。 此外，废用事件后的肌肉恢复在老年人中受损。因此， 面对快速增长的老龄化人口，需要进一步了解其背后的细胞机制。 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） 关键的重要性，以最佳恢复肌肉大小后，一段时间的废用，然而，他们的作用下，这样的 令人惊讶的是，还没有阐明老化骨骼肌的条件。因此，使用完善的 小鼠模型的肌肉废用和再生，我们已经产生了令人信服的初步数据表明， 老年小鼠肌肉再生受损，并伴有巨噬细胞免疫反应改变 和恢复过程中骨骼肌的募集。在目前的建议中，我们建议进行一项 老年和年轻小鼠肌肉巨噬细胞（和其他免疫细胞）反应的广泛时间过程 从废弃中恢复过来我们还将确定是否抑制巨噬细胞募集的年轻小鼠将导致 在从废用中恢复老年小鼠的表型特征中。我们将利用联合独特的 流式细胞仪和单细胞RNA测序的方法来广泛地解决这些问题。这些数据将 是研究巨噬细胞和其他细胞的上游介质的额外机制研究的基础。 在从废用中恢复期间的免疫细胞反应，同时还使用新的免疫疗法来优化肌肉 老年肌肉的恢复