Changes in macrophage immunometabolism as a marker of skeletal muscle dysfunction across the lifespan.
Changes in macrophage immunometabolism as a marker of skeletal muscle dysfunction across the lifespan.
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DOI：
10.18632/aging.204750
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发表时间：
2023-05-25
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老年人最明显的变化之一是由于骨骼肌功能下降而导致的力量和活动能力丧失，导致称为肌肉减少症的多因素条件。虽然显着的临床变化开始表现在先进的年龄，最近的研究表明，在细胞和分子水平的变化之前，肌肉减少症的病理学。通过利用小鼠骨骼肌在整个生命周期中的单细胞转录组图谱，我们确定了中年期间出现的免疫衰老的明显迹象。更重要的是，中年巨噬细胞表型的变化可以解释细胞外基质成分的变化，特别是胶原蛋白合成，这有助于纤维化和整体肌无力与高龄。我们的研究结果显示了一种新的范式，即骨骼肌功能障碍是由中年小鼠出现临床症状之前组织驻留巨噬细胞的变化驱动的，通过调节免疫代谢提供了一种新的治疗方法。
One of the most pronounced changes in the elderly is loss of strength and mobility due to the decline of skeletal muscle function, resulting in a multifactorial condition termed sarcopenia. Although significant clinical changes begin to manifest at advanced ages, recent studies have shown that changes at the cellular and molecular level precede the symptomatology of sarcopenia. By utilizing a single-cell transcriptomic atlas of mouse skeletal muscle across the lifespan, we identified a clear sign of immune senescence that presents during middle age. More importantly, the change in macrophage phenotype in middle age may explain the changes in extracellular matrix composition, especially collagen synthesis, that contributes to fibrosis and overall muscle weakness with advanced age. Our results show a novel paradigm whereby skeletal muscle dysfunction is driven by alterations in tissue-resident macrophages before the appearance of clinical symptoms in middle-aged mice, providing a new therapeutic approach via regulation of immunometabolism.