NFκB Regulates Muscle Development and Mitochondrial Function.

yyy Nuclear factor (NF)kappa B is a transcription factor that controls immune and inflammatory signaling pathways. In skeletal muscle, NF kappa B 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 NF kappa B on mitochondrial function and its relationship with muscle mass across the life span, we study a mouse model with muscle-specific NF kappa B suppression (muscle-specific I kappa B alpha super-repressor [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. NF kappa B inactivation downregulated expression of PPARGC1A, and upregulated TFEB and PPARGC1B. NF kappa B inactivation also 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 NF kappa B pathway plays an important role in muscle development and growth. The extent to which NF kappa B suppression alters mitochondrial function is age dependent and muscle specific. Finally, mitochondrial function and muscle mass are tightly associated in both genotypes and across the life span.