PDF(Pubmed)
Abstract：
Senescence of skeletal muscle (SkM) has been a primary contributor to senior weakness and disability in recent years. The gradually declining SkM function associated with senescence has recently been connected to an imbalance between damage and repair. Macrophages (Mac) are involved in SkM aging, and different macrophage subgroups hold different biological functions. Through comprehensive single-cell transcriptomic analysis, we first compared the metabolic pathways and biological functions of different types of cells in young (Y) and old (O) mice SkM. Strikingly, the Mac population in mice SkM was also explored, and we identified a unique Mac subgroup in O SkM characterized by highly expressed SPP1 with strong senescence and adipogenesis features. Further work was carried out on the metabolic and biological processes for these Mac subgroups. Besides, we verified that the proportion of the SPP1+ Mac was increased significantly in the quadriceps tissues of O mice, and the senotherapeutic drug combination dasatinib + quercetin (D + Q) could dramatically reduce its proportion. Our study provides novel insight into the potential role of SPP1+ Mac in SkM, which may serve as a senotherapeutic target in SkM aging.
摘要：
近年来，骨骼肌衰老（SkM）一直是导致老年人虚弱和残疾的主要原因。与衰老相关的逐渐下降的SkM功能最近与损伤和修复之间的不平衡有关。巨噬细胞(Mac)参与SkM老化，不同的巨噬细胞亚群具有不同的生物学功能。通过全面的单细胞转录组学分析，我们首先比较了年轻（Y）和老年（O）小鼠SkM中不同类型细胞的代谢途径和生物学功能。引人注目的是，也探索了老鼠SkM中的Mac种群，我们在OSkM中确定了一个独特的Mac亚群，其特征是高表达的SPP1具有强烈的衰老和脂肪生成特征。对这些Mac亚群的代谢和生物过程进行了进一步的研究。此外,我们验证了在O小鼠的股四头肌组织中SPP1+Mac的比例显着增加，治疗药物达沙替尼+槲皮素(D+Q)可以显著降低其比例。我们的研究为SPP1+Mac在SkM中的潜在作用提供了新的见解，这可能是SkM衰老的一个治疗靶点。
