NFκB is a transcription factor that controls immune and inflammatory signaling pathways. In skeletal muscle, NFκB has been implicated in the regulation of metabolic processes and tissue mass; yet, its affects on mitochondrial function in this tissue are unclear. To investigate the role of NFκB on mitochondrial function and its relationship with muscle mass across the lifespan, we study a mouse model with muscle-specific NFκB suppression (MISR mice). In wild type mice there was a natural decline in muscle mass with aging that was accompanied by decreased mitochondrial function and mRNA expression of electron transport chain subunits. NFκB inactivation downregulated expression of PPARGC1A, while upregulating TFEB and PPARGC1B, as well as decreased gastrocnemius (but not soleus) muscle mass in early life (1-6 months old). Lower oxygen consumption rates occurred in gastrocnemius and soleus muscles from young MISR mice, whereas soleus (but not gastrocnemius) muscles from old MISR mice displayed increased oxygen consumption compared to age-matched controls. We conclude that the NFκB pathway plays an important role in muscle development and growth. The extent to which NFκB suppression alters mitochondrial function is age-dependent and muscle-specific. Lastly, mitochondrial function and muscle mass are tightly associated in both genotypes and across the lifespan.

中文翻译：

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NFκB调节肌肉发育和线粒体功能。

NFκB是控制免疫和炎症信号通路的转录因子。在骨骼肌中，NFκB已经参与了代谢过程和组织质量的调节。然而，它对该组织中线粒体功能的影响尚不清楚。为了研究NFκB在线粒体功能中的作用及其与整个寿命中肌肉质量的关系，我们研究了具有肌肉特异性NFκB抑制作用的小鼠模型（MISR小鼠）。在野生型小鼠中，随着年龄的增长，肌肉质量自然下降，伴随着线粒体功能下降和电子转运链亚基的mRNA表达下降。NFκB失活下调了PPARGC1A的表达，同时上调了TFEB和PPARGC1B，并降低了早期（1-6个月大）腓肠肌（但不是比目鱼肌）的肌肉质量。与年龄相匹配的对照组相比，年轻的MISR小鼠的腓肠肌和比目鱼肌的耗氧率较低，而老年MISR小鼠的比目鱼肌（而非腓肠肌）的耗氧量增加。我们得出结论，NFκB通路在肌肉发育和生长中起着重要作用。NFκB抑制作用改变线粒体功能的程度取决于年龄和肌肉特异性。最后，线粒体功能和肌肉质量在两种基因型和整个寿命中都紧密相关。NFκB抑制作用改变线粒体功能的程度取决于年龄和肌肉特异性。最后，线粒体功能和肌肉质量在两种基因型和整个寿命中都紧密相关。NFκB抑制作用改变线粒体功能的程度取决于年龄和肌肉特异性。最后，线粒体功能和肌肉质量在两种基因型和整个寿命中都紧密相关。