Notch Reduces Muscle Injury in Aged Mice Following Downhill Running

Abstract

PURPOSE: It Is known that Notch signaling regulates skeletal muscle repair and is suggested to be inhibited in aged muscle. However, little is known about the effects of Notch on muscle injury following exercise in aged mice. The purpose of this project is to determine the impact of Notch signaling on aged skeletal muscle injury following downhill running (DHR). METHODS: C57B/J6 and CBF1 mice (20-25 mo old) served as controls or performed a bout of DHR (~11m/min,-15% grade) until exhaustion. A Notch inhibitor (GSI) or Notch force-activator (FA) reagent were injected into the left gastrocnemius and PBS (control) was injected into right gastrocnemius starting at 24h post exercise. Haemotoxylin and Eosin staining was used to quantify muscle injury. RESULTS: In C57B/J6 mice, DHR induced injury in GSI (4D: P = <0.001; 5D: P = <0.001; and 6D: P = <0.001) and PBS-treated (4D: P = 0.016; 5D: P = 0.004) muscles. Relative to PBS, GSI increased muscle injury two-fold 4D-6D post-exercise (P < 0.001). DHR did not induce significant muscle injury in CBF1 mice (P = 0.12). FA reduced muscle injury compared to PBS (P = 0.04). CONCLUSIONS: Notch inhibition appears to increase muscle injury post-exercise, while Notch activation appears to reduce injury. Supported bv UNC Charlotte Faculty Research Grant.