Paliwal Preeti, Pishesha Novalia, Wijaya Denny, Conboy Irina M
Department of Bioengineering, University of California, Berkeley, CA 94720, USA.
Aging (Albany NY). 2012 Aug;4(8):553-66. doi: 10.18632/aging.100477.
Skeletal muscle regeneration following injury is accompanied by rapid infiltration of macrophages, which play a positive role in muscle repair. Increased chronic inflammation inhibits the regeneration of dystrophic muscle, but the properties of inflammatory cells are not well understood in the context of normal muscle aging. This work uncovers pronounced age-specific changes in the expression of osteopontin (OPN) in CD11b+ macrophages present in the injured old muscle as well as in the blood serum of old injured mice and in the basement membrane surrounding old injured muscle fibers. Furthermore, young CD11b+ macrophages enhance regenerative capacity of old muscle stem cells even when old myofibers and old sera are present; and neutralization of OPN similarly rejuvenates the myogenic responses of old satellite cells in vitro and notably, in vivo. This study highlights potential mechanisms by which age related inflammatory responses become counter-productive for muscle regeneration and suggests new strategies for enhancing muscle repair in the old.
损伤后的骨骼肌再生伴随着巨噬细胞的快速浸润，巨噬细胞在肌肉修复中发挥着积极作用。慢性炎症的增加会抑制营养不良性肌肉的再生，但在正常肌肉衰老的情况下，炎症细胞的特性尚未得到充分了解。这项研究揭示了受伤老龄肌肉中存在的CD11b +巨噬细胞、老龄受伤小鼠的血清以及老龄受伤肌纤维周围基底膜中骨桥蛋白（OPN）表达的明显年龄特异性变化。此外，即使存在老龄肌纤维和老龄血清，年轻的CD11b +巨噬细胞也能增强老龄肌肉干细胞的再生能力；OPN的中和同样能在体外显著地在体内恢复老龄卫星细胞的成肌反应。这项研究突出了与年龄相关的炎症反应对肌肉再生产生反作用的潜在机制，并提出了增强老龄肌肉修复的新策略。
