Javadov S, Jang S, Rodriguez-Reyes N, Rodriguez-Zayas AE, Soto Hernandez J, Krainz T, Wipf P, Frontera W. Mitochondria-targeted antioxidant preserves contractile properties and mitochondrial function of skeletal muscle in aged rats. Oncotarget. 2015 Sep 22. PMID: 26415224 [PubMed]
Mitochondrial dysfunction plays a central role in the pathogenesis of sarcopenia associated with a loss of mass and activity of skeletal muscle. In addition to energy deprivation, increased mitochondrial ROS damage proteins and lipids in aged skeletal muscle. Therefore, prevention of mitochondrial ROS is important for potential therapeutic strategies to delay sarcopenia. This study elucidates the pharmacological efficiency of the new developed mitochondria-targeted ROS and electron scavenger, XJB-5-131 (XJB) to restore muscle contractility and mitochondrial function in aged skeletal muscle. Male adult (5-month old) and aged (29-month old) Fischer Brown Norway (F344/BN) rats were treated with XJB for four weeks and contractile properties of single skeletal muscle fibres and activity of mitochondrial ETC complexes were determined at the end of the treatment period. XJB-treated old rats showed higher muscle contractility associated with prevention of protein oxidation in both muscle homogenate and mitochondria compared with untreated counterparts. XJB-treated animals demonstrated a high activity of the respiratory complexes I, III, and IV with no changes in citrate synthase activity. These data demonstrate that mitochondrial ROS play a causal role in muscle weakness, and that a ROS scavenger specifically targeted to mitochondria can reverse age-related alterations of mitochondrial function and improve contractile properties in skeletal muscle.