Preliminary findings on the enhancement of skeletal muscle structure and function in aged male mice by P7C3 activation of nicotinamide phosphoribosyl transferase (NAMPT).

UNLABELLED: Nicotinamide phosphoribosyl transferase (NAMPT) activation is a key enzyme in the NAD+ salvage pathway that mediates major metabolic changes in skeletal muscle and during aging. The Nampt activator P7C3 provides beneficial effects to both cardiac and skeletal muscle in diabetes, but the effects on aging remain unknown. HYPOTHESIS: In the present study we hypothesized that Nampt activation via P7C3 administration would enhance skeletal muscle structure and function in aged mice. METHODS: Two-year-old male C57BL/6 mice were treated daily with 10 mg/Kg body weight P7C3 or an equivalent volume of vehicle (DMSO) for 4 weeks. Measurements of ex vivo force frequency relationship (FFR), grip strength, myofiber cross-sectional area (CSA), and Western blotting were conducted to assess muscle responses in old age. RESULTS: FFR showed P7C3 provided clear improvement in muscle contractility in EDL and Soleus, though muscle fatigue was unaffected. Volitional grip strength was maintained after 4 weeks of treatment with P7C3, while it declined in the vehicle treatment group. Distribution of muscle fiber CSA in the Tibialis anterior muscle was significantly shifted toward larger fibers in P7C3 treated group. Nampt expression as well as p-Akt/total-Akt protein levels were increased in EDL muscle from the mice treated with P7C3. CONCLUSION: Overall, the present study demonstrates for the first time that Nampt activation via P7C3 injections allows for improved fast and slow skeletal muscle function in aged mice with increased muscle quality, myofiber CSA and preserved grip strength.