NFκB Regulates Muscle Development and Mitochondrial Function.
Valentine JM, Li ME, Shoelson SE, Zhang N, Reddick RL, Musi N
J Gerontol A Biol Sci Med Sci. 2018 Nov 13. doi: 10.1093/gerona/gly262. [Epub ahead of print]
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.