AGE-DEPENDENT CHANGES IN THE PRODUCTION OF MITOCHONDRIAL REACTIVE OXYGEN SPECIES IN HUMAN SKELETAL MUSCLE

Abstract

A decrease in muscle mass and its functionality (strength, performance and insulin sensitivity) is one of the integral signs of aging. One of the triggers of aging is an increase in the production of mitochondrial reactive oxygen species. In our study, for the first time, age-dependent changes in the production of mitochondrial reactive oxygen species associated with a decrease in the proportion of mitochondria-associated hexokinase-2 in human skeletal muscle were studied. For this purpose, a biopsy from m. vastus lateralis in 10 young healthy volunteers and 70 patients (26-85 years old) with long-term primary arthrosis of the knee/hip joint was taken. It turned out that aging (comparison of different groups of patients), in contrast to inactivity/chronic inflammation (comparison of young healthy people and young patients), causes a pronounced increase in peroxide production by isolated mitochondria. This correlated with an age-dependent disruption of the mechanism of mild depolarization of mitochondria, namely with the distribution of hexokinase between the mitochondrial and cytosolic fractions, a decrease in the rate of coupled respiration of isolated mitochondria and respiration stimulated by glucose (the substrate of hexokinase). It is discussed that these changes may be caused by an age-dependent decrease in the content of cardiolipin, a potential regulator of the mitochondrial microcompartment containing hexokinase. The results obtained contribute to a deeper understanding of age-related pathogenetic processes in skeletal muscles and open prospects for the search for pharmacological/physiological approaches to the correction of these pathologies.