title: Liver specific expression of Cu/ZnSOD extends the lifespan of Sod1 null mice.
abstract: Genetic ablation of CuZn-superoxide dismutase (Sod1) in mice (Sod1(-/-) mice) leads to shortened lifespan with a dramatic increase in hepatocellular carcinoma and accelerated aging phenotypes, including early onset sarcopenia. To study the tissue specific effects of oxidative stress in the Sod1(-/-) mice, we generated mice that only express the human SOD1 gene specifically in the liver of Sod1(-/-) mice (Sod1(-/-)/hSOD1(alb) mice). Expression of hSOD1 in the liver of Sod1(-/-) mice improved liver function, reduced oxidative damage in liver, and partially restored the expression of several genes involved in tumorigenesis, which are abnormally expressed in the livers of the Sod1(-/-) mice. However, liver specific expression of hSOD1 did not prevent the loss of body weight and muscle mass and alterations in the structure of neuromuscular junctions. The expression of hSOD1 in the liver of Sod1(-/-) mice significantly improved the lifespan of Sod1(-/-) mice; however, the lifespan of the Sod1(-/-)/hSOD1(alb) mice was still significantly shorter than wild type mice.
authors.affiliation: Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Yiqiang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Departments of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA. Electronic address: LiuY2@uthscsa.edu.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Departments of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA. Electronic address: walshme125@gmail.com.
authors.forename: Michael
authors.initials: M
authors.lastname: Walsh
authors.affiliation: Departments of Epidemiology and Biostatistics, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA. Electronic address: BOKOV@uthscsa.edu.
authors.forename: Alex
authors.initials: A
authors.lastname: Bokov
authors.affiliation: Departments of Pathology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA; Geriatric Research, Education and Clinical Center (GRECC), South Texas Veterans Health Care System, San Antonio, Texas, USA.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ikeno
authors.affiliation: School of Applied Physiology, Georgia Institute of Technology, Atlanta, GA, USA. Electronic address: young.jang@gatech.edu.
authors.forename: Young C
authors.initials: YC
authors.lastname: Jang
authors.affiliation: Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR, USA. Electronic address: Viviana.Perez@oregonstate.edu.
authors.forename: Viviana I
authors.initials: VI
authors.lastname: Perez
authors.affiliation: Oklahoma Medical Research Foundation, Oklahoma City, OK, USA; Oklahoma City VA Medical Center, Oklahoma City, OK, USA. Electronic address: Holly-VanRemmen@omrf.org.
authors.forename: Holly
authors.initials: H
authors.lastname: Van Remmen
authors.affiliation: Oklahoma City VA Medical Center, Oklahoma City, OK, USA; Oklahoma University Health Science Center, Oklahoma City, OK, USA. Electronic address: arlan-richardson@ouhsc.edu.
authors.forename: Arlan
authors.initials: A
authors.lastname: Richardson
mesh_terms: D000818:Animals; D006801:Humans; D008099:Liver / Q000201:enzymology*; D008136:Longevity; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity; D000072105:Superoxide Dismutase-1 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C000606290:SOD1 protein, human; D000072105:Superoxide Dismutase-1
keywords: CuZnSOD; Lifespan; Liver-specific transgenic mice; Oxidative stress
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