Aging impairs mouse skeletal muscle macrophage polarization and muscle-specific abundance during recovery from disuse
Aging impairs mouse skeletal muscle macrophage polarization and muscle-specific abundance during recovery from disuse
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DOI：
10.1152/ajpendo.00422.2018
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发表时间：
2019-07-01
影响因子：
5.1
通讯作者：
Drummond, Micah J.
中科院分区：
文献类型：
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作者：
Reidy, Paul T.;McKenzie, Alec, I;Drummond, Micah J.
废用事件后老化肌肉的恢复受损是老年人面临的一个未解决的问题。尽管对年轻动物的研究表明，废用事件后骨骼肌的快速再生需要骨骼肌巨噬细胞的协调参与，但这种现象尚未被彻底测试为衰老中肌肉恢复受损的解释。为了检验这一假设，在后肢卸载（HU）2周后以及HU后重新加载4天（RL 4）和7天（RL 7）后，检查年轻（4-5月龄）和老年（24-26月龄）雄性小鼠作为对照。收获肌肉以通过免疫荧光评估肌肉重量、肌纤维特异性横截面积和骨骼肌巨噬细胞。在腓肠肌和比目鱼肌（在RL 4）单细胞悬浮液上使用流式细胞术以免疫表型骨骼肌巨噬细胞。我们的数据表明，与年轻小鼠相比，老年小鼠废用后肌肉再生受损，其特征在于不同的肌肉巨噬细胞极化模式和肌肉特异性巨噬细胞丰度。在再负荷期间，年轻小鼠表现出典型的M1样（MHC II（+）CD 206（-））巨噬细胞的增加，这导致M2样巨噬细胞（MHC II（-）CD 206（+））的百分比增加;然而。老年小鼠没有表现出这种模式。在RL 4。比目鱼肌显示随着年龄的增长巨噬细胞丰度降低。一起这些数据表明，在从废用中恢复期间，老化肌肉中失调的巨噬细胞表型模式可能与受损的肌肉生长有关。需要进一步的研究来确定老年人在废用再生过程中巨噬细胞反应失调是否与招募或激活特定免疫细胞的能力降低有关。
Impaired recovery of aged muscle following a disuse event is an unresolved issue facing the older adult population. Although investigations in young animals have suggested that rapid regrowth of skeletal muscle following a disuse event entails a coordinated involvement of skeletal muscle macrophages, this phenomenon has not yet been thoroughly tested as an explanation for impaired muscle recovery in aging. To examine this hypothesis, young (4-5 mo) and old (24-26 mo) male mice were examined as controls following 2 wk of hindlimb unloading (HU) and following 4 (RL4) and 7 (RL7) days of reloading after HU. Muscles were harvested to assess muscle weight, myofiber-specifc cross-sectional area, and skeletal muscle macrophages via immunofluorescence. Flow cytometry was used on gastrocnemius and soleus muscle (at RL4) single-cell suspensions to immunophenotype skeletal muscle macrophages. Our data demonstrated impaired muscle regrowth in aged compared with young mice following disuse, which was characterized by divergent muscle macrophage polarization patterns and muscle-specifc macrophage abundance. During reloading, young mice exhibited the classical increase in M1-like (MHC II(+)CD206(-)) macrophages that proceeded the increase in percentage of M2-like macrophages (MHC II(-)CD206(+)); however. old mice did not demonstrate this pattern. Also, at RL4. the soleus demonstrated reduced macrophage abundance with aging. Together. these data suggest that dysregulated macrophage phenotype patterns in aged muscle during recovery from disuse may be related to impaired muscle growth. Further investigation is needed to determine whether the dysregulated macrophage response in the old during regrowth from disuse is related to a reduced ability to recruit or activate specific immune cells.