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

摘要 老年人容易经历肌肉停用的时期，导致肌肉萎缩和虚弱。 此外，老年人在停用事件后的肌肉恢复会受到损害。因此，优先考虑的是 面对快速增长的老龄化人口，有必要进一步了解背后的细胞机制 随着年龄的增长，受损的肌肉会再生。巨噬细胞和其他免疫细胞群(例如T细胞)是 然而，在停用一段时间后以最佳方式恢复肌肉大小至关重要，但在这种情况下，它们的作用 令人惊讶的是，骨骼肌老化的情况还没有被阐明。因此，使用一种成熟的 小鼠肌肉废用和再生的模型，我们已经产生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 并在恢复期间在骨骼肌中进行募集。在目前的建议中，我们建议进行一项 老年和幼年小鼠肌肉巨噬细胞(和其他免疫细胞)反应的广泛时间进程 在从废弃中恢复的过程中。我们还将确定是否会抑制幼鼠的巨噬细胞募集 在从废用中恢复的老年小鼠的表型特征中。我们将使用组合唯一 流式细胞仪和单细胞RNA测序的方法广泛地解决了这些问题。这些数据将 为研究巨噬细胞和其他上游介质的其他机制研究奠定基础 废用恢复过程中的免疫细胞反应，同时使用新的免疫疗法来优化肌肉 老肌肉的恢复。

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.