Targeting macrophage polarization to optimize muscle regrowth from disuse atrophy

摘要 许多老年人在停用后肌肉恢复受到损害，这可能会增加摔倒的风险。 骨折和残疾。我们已经证明，肌肉巨噬细胞在再生期间是失调的。 在衰老的肌肉中发生了一次停用事件。因此，我们提出了一系列优雅的、临床前的小鼠 确定各种免疫调节疗法的有效性并确定特异性的实验 老年性骨骼肌再生过程中与年龄相关的肌肉免疫失调机制 停用。我们将利用最先进的方法对肌肉巨噬细胞(FAC，单细胞RNA)进行表型分析 测序、免疫荧光)与小鼠遗传学和骨移植实验相结合，广泛 回答这些问题。产生的数据将是识别潜在机制的第一个此类数据 废用性萎缩后再生长过程中老化肌肉中巨噬细胞的异常调节，同时还测试了 免疫调节增强了老年人的肌肉和功能恢复。

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.