Darcy L. Johannsen, Eric Ravussin  Cell Metabolism 

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Can Increased Muscle ROS Scavenging Keep Older Animals Young and Metabolically Fit?  Darcy L. Johannsen, Eric Ravussin  Cell Metabolism  Volume 12, Issue 6, Pages 557-558 (December 2010) DOI: 10.1016/j.cmet.2010.11.014 Copyright © 2010 Elsevier Inc. Terms and Conditions

Figure 1 Characteristics of Skeletal Muscle Mitochondria in Young and Older WT Mice and in Older Mice with Overexpression of Human Catalase in Mitochondria The electron transport system (ETS) of the inner mitochondrial membrane is the primary site of reactive oxygen species (ROS) production and therefore the main source of oxidative stress (damage to proteins, lipids, and DNA) in the mitochondria and in the cell. Free radical superoxide anions (O2.−) are generated when electrons are donated from complexes I and III of the ETS to O2 instead of the appropriate ETS subunit. 2%–4% of total oxygen consumption may go toward the production of ROS instead of energy as ATP. Scavenging enzymes represent an important mitochondrial mechanism against oxidative stress by neutralizing O2.− within the mitochondrial matrix (superoxide dismutase; MnSOD = SOD2) and catalyzing the reduction of mitochondrial SOD2-generated H2O2 to nontoxic H2O in the mitochondria and the cell (glutathione peroxidase and catalase). Mitochondria in young muscle (upper panel) are numerous, efficient, and associated with less intramyocellular lipid (IMCL) and good insulin sensitivity. With age (middle panel), muscle mitochondria become less numerous and seem to develop impaired function associated with reduced oxidative capacity, likely causing an increase in IMCL and its metabolites (DAG and ceramides). Together, these adverse changes result in impaired insulin sensitivity. By overexpressing the human catalase in skeletal muscle mitochondria, Lee et al. (Lee et al., 2010) showed that all of these impairments in aged muscle are reversed, including an improvement in insulin sensitivity (bottom panel, red). Cell Metabolism 2010 12, 557-558DOI: (10.1016/j.cmet.2010.11.014) Copyright © 2010 Elsevier Inc. Terms and Conditions