MnSOD deficiency results in elevated oxidative stress and decreased mitochondrial function but does not lead to muscle atrophy during aging
Michael S. Lustgarten
Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
The Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
Search for more papers by this authorYoungmok C. Jang
The Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
Search for more papers by this authorYuhong Liu
Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
Search for more papers by this authorWenbo Qi
The Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
Search for more papers by this authorYuejuan Qin
Department of Medicine, Hematology and Medical Oncology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
Search for more papers by this authorPatricia L. Dahia
Department of Medicine, Hematology and Medical Oncology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
Search for more papers by this authorYun Shi
Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
Search for more papers by this authorArunabh Bhattacharya
The Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
Search for more papers by this authorFlorian L. Muller
Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
Search for more papers by this authorTakahiko Shimizu
Research Team for Molecular Biomarkers-Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan
Search for more papers by this authorTakuji Shirasawa
Research Team for Molecular Biomarkers-Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan
Search for more papers by this authorArlan Richardson
The Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
South Texas Veterans Health Care System, Audie L. Murphy Division, San Antonio, Texas
Search for more papers by this authorHolly Van Remmen
The Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
South Texas Veterans Health Care System, Audie L. Murphy Division, San Antonio, Texas
Search for more papers by this authorMichael S. Lustgarten
Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
The Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
Search for more papers by this authorYoungmok C. Jang
The Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
Search for more papers by this authorYuhong Liu
Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
Search for more papers by this authorWenbo Qi
The Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
Search for more papers by this authorYuejuan Qin
Department of Medicine, Hematology and Medical Oncology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
Search for more papers by this authorPatricia L. Dahia
Department of Medicine, Hematology and Medical Oncology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
Search for more papers by this authorYun Shi
Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
Search for more papers by this authorArunabh Bhattacharya
The Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
Search for more papers by this authorFlorian L. Muller
Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
Search for more papers by this authorTakahiko Shimizu
Research Team for Molecular Biomarkers-Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan
Search for more papers by this authorTakuji Shirasawa
Research Team for Molecular Biomarkers-Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan
Search for more papers by this authorArlan Richardson
The Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
South Texas Veterans Health Care System, Audie L. Murphy Division, San Antonio, Texas
Search for more papers by this authorHolly Van Remmen
The Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
South Texas Veterans Health Care System, Audie L. Murphy Division, San Antonio, Texas
Search for more papers by this authorSummary
In a previous study, we reported that a deficiency in MnSOD activity (approximately 80% reduction) targeted to type IIB skeletal muscle fibers was sufficient to elevate oxidative stress and to reduce muscle function in young adult mice (TnIFastCreSod2fl/fl mice). In this study, we used TnIFastCreSod2fl/fl mice to examine the effect of elevated oxidative stress on mitochondrial function and to test the hypothesis that elevated oxidative stress and decreased mitochondrial function over the lifespan of the TnIFastCreSod2fl/fl mice would be sufficient to accelerate muscle atrophy associated with aging. We found that mitochondrial function is reduced in both young and old TnIFastCreSod2fl/fl mice, when compared with control mice. Complex II activity is reduced by 47% in young and by approximately 90% in old TnIFastCreSod2fl/fl mice, and was found to be associated with reduced levels of the catalytic subunits for complex II, SDHA and SDHB. Complex II-linked mitochondrial respiration is reduced by approximately 70% in young TnIFastCreSod2fl/fl mice. Complex II-linked mitochondrial Adenosine-Tri-Phosphate (ATP) production is reduced by 39% in young and was found to be almost completely absent in old TnIFastCreSod2fl/fl mice. Furthermore, in old TnIFastCreSod2fl/fl mice, aconitase activity is almost completely abolished; mitochondrial superoxide release remains > 2-fold elevated; and oxidative damage (measured as F2- isoprostanes) is increased by 30% relative to age-matched controls. These data show that despite elevated skeletal muscle–specific mitochondrial oxidative stress, oxidative damage, and complex II-linked mitochondrial dysfunction, age-related muscle atrophy was not accelerated in old TnIFastCreSod2fl/fl mice, suggesting mitochondrial oxidative stress may not be causal for age-related muscle atrophy.
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