Skeletal muscle aging: Role of reactive oxygen species

Abstract

During aging, a significant loss of skeletal muscle mass and function occurs that can have a dramatic impact on the quality of life of older individuals. The processes underlying this loss of mass and function are unknown, but a chronic increase in cellular superoxide has been implicated in the contributory mechanisms. Mitochondria are a major cellular site for superoxide generation at complexes I or III of the electron transport chain. Within the mitochondrial matrix, superoxide is converted to hydrogen peroxide though activity of Mn-superoxide dismutase. A portion of the superoxide generated at complex III is also released into the mitochondrial intermembrane space, which contains a recently identified copper, zinc superoxide dismutase (Cu,ZnSOD). Deletion of Cu,ZnSOD has been shown to lead to a phenotype of accelerated age-related loss of skeletal muscle mass and function, although it is unclear whether loss of the enzyme in the intermembrane space or cytosol is important in this respect. It is hypothesized that the processes underlying loss of muscle mass and function in the Cu,ZnSOD knockout mice provide a model that can inform identification of the processes that occur during normal aging.