Changes In Mitochondrial Function With Aging Do Not Translate To Degree Of Atrophy In Senescent Sol And Edl Muscle

Abstract

Fast twitch (FT) muscles are thought to be more susceptible to the age-related reduction in muscle mass and function known as sarcopenia. Mitochondrial function changes with aging in several ways that could be important to sarcopenia. For example, elevated ROS emission, reduced ATP synthesis and reduced Ca2+ retention can lead to mitochondrial permeability transition pore (mPTP) opening, and ultimately to apoptosis, which is speculated to contribute to sarcopenia. Although mitochondria from FT muscle exhibit greater ROS production, which may render FT muscle more susceptible to atrophy, it is unknown whether aging differentially affects mitochondrial function between slow twitch (ST) and FT muscles in ways that relate to the progression of sarcopenia. PURPOSE: To clarify the role of mitochondria in the atrophy of FT versus ST muscle with aging, we examined mitochondrial function in the largely FT extensor digitorum longus (EDL) muscle and the largely ST soleus (Sol) muscle. We hypothesized that mitochondrial dysfunction with aging would be greater in EDL and that this would translate to a greater atrophy. METHODS: Mitochondrial function was examined in permeabilized myofibers prepared from the SOL and EDL of young adult and senescent male F344×BN rats. RESULTS: Respiratory capacity in EDL was maintained with age, whereas it declined in Sol (30.5%, p <0.01). This latter finding was nullified when normalized to citrate synthase (CS) activity, indicating that mitochondrial content not function is responsible for reduced respiration in Sol. H2O2 emission increased with age in EDL (22 %, p < 0.001) but not in SOL. When normalized to CS H2O2 emission increased in EDL and SOL, 28% and 25% respectively (p < 0.05), indicating that ROS production per mitochondrion increases with age in both muscles. Calcium retention capacity was reduced (21.4%, p < 0.05) and time to pore opening was faster (27.9%, p < 0.001) with age in the EDL but not in the SOL, suggesting sensitization of the mPTP to opening in the EDL with aging. Despite these differences in mitochondrial function, muscle atrophy was strikingly similar (20%) in each muscle. CONCLUSIONS: Our results showed larger changes in mitochondrial function with aging in the FT EDL; however, this did not translate to greater muscle atrophy, arguing against a mitochondrial explanation for sarcopenia.