Age-associated NF-κB signaling in myofibers alters the satellite cell niche and re-strains muscle stem cell function.
Age-associated NF-κB signaling in myofibers alters the satellite cell niche and re-strains muscle stem cell function.
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DOI：
10.18632/aging.101098
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发表时间：
2016-11-14
期刊：
影响因子：
--
通讯作者：
Wagers AJ
中科院分区：
文献类型：
--
作者：
Oh J;Sinha I;Tan KY;Rosner B;Dreyfuss JM;Gjata O;Tran P;Shoelson SE;Wagers AJ
骨骼肌是一种高度再生的组织，但随着年龄的增长，肌肉修复的潜力越来越大。在这项研究中，我们证明，增加NF-κB活性在老年肌纤维有助于减少肌原性潜力，其相关的卫星细胞。我们进一步研究了肌肉卫星细胞或肌纤维中NF-κB信号传导的遗传调节对损伤后恢复的影响。这些研究表明，分化肌纤维中的NF-κB活性足以通过细胞非自主机制驱动肌肉再生细胞的功能障碍。抑制肌纤维中的NF-κB或其下游靶点磷脂酶A2可挽救老年肌肉中的肌肉再生潜力。此外，全身给予水杨酸钠（一种FDA批准的NF-κB抑制剂）可降低炎症基因表达，改善老化肌肉的修复。总之，这些研究确定了一种独特的NF-κB调节的非细胞自主机制，通过该机制，干细胞功能与脂质信号传导和稳态相关，并提供了重要的新靶点来刺激老年个体的肌肉修复。
Skeletal muscle is a highly regenerative tissue, but muscle repair potential is increasingly compromised with advancing age. In this study, we demonstrate that increased NF-κB activity in aged muscle fibers contributes to diminished myogenic potential of their associated satellite cells. We further examine the impact of genetic modulation of NF-κB signaling in muscle satellite cells or myofibers on recovery after damage. These studies reveal that NF-κB activity in differentiated myofibers is sufficient to drive dysfunction of muscle regenerative cells via cell-non-autonomous mechanisms. Inhibition of NF-κB, or its downstream target Phospholipase A2, in myofibers rescued muscle regenerative potential in aged muscle. Moreover, systemic administration of sodium salicylate, an FDA-approved NF-κB inhibitor, decreased inflammatory gene expression and improved repair in aged muscle. Together, these studies identify a unique NF-κB regulated, non-cell autonomous mechanism by which stem cell function is linked to lipid signaling and homeostasis, and provide important new targets to stimulate muscle repair in aged individuals.
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