A 12-Week Strength Training Improves Mitochondrial Respiration, H2O2 Emission and Skeletal Muscle Integrity in Women With Myotonic Dystrophy Type 1.

BACKGROUND: Myotonic dystrophy type 1 (DM1) is caused by expanded CTG repeats in the DMPK gene, causing the accumulation of toxic RNA that sequesters RNA-binding proteins. Clinically, DM1 is characterized by progressive muscle weakness and atrophy, resulting in reduced physical capacity and quality of life. Recent evidence implicates mitochondrial dysfunction in DM1 pathophysiology. While aerobic exercise has been shown to improve skeletal muscle and mitochondrial health in individuals with DM1, the benefits of strength training remain unexplored. OBJECTIVES: We investigated the effects of a 12-week strength training program on mitochondrial respiration, reactive oxygen species (ROS) production and muscle integrity in women with DM1. METHODS: Vastus lateralis muscle biopsies were collected pre- and post-training in participants with DM1 and once in unaffected/untrained individuals. Mitochondrial respiration and hydrogen peroxide emission (marker of ROS production) were assessed in permeabilized myofibers, while OXPHOS protein contents were quantified by immunoblotting and immunofluorescence. Markers of myofiber denervation (NCAM+) and integrity (centrally located myonuclei, damaged laminin, nuclear clumps) were assessed on histological sections. RESULTS: At baseline, DM1 participants exhibited lower mitochondrial respiration compared to unaffected individuals. Strength training significantly improved mitochondrial respiration and content in DM1 participants. At baseline, absolute ROS production was lower, while ROS production normalized to oxygen consumption (free radical leak) was higher, in DM1. Histological signs of denervation and altered muscle integrity were observed. Strength training partially normalized mitochondrial free radical leak and restored some markers of myofiber integrity. CONCLUSION: Collectively, our results indicate that strength training enhances mitochondrial health and improves myofiber integrity in women with DM1.