The overexpression of major antioxidant enzymes does not extend the lifespan of mice

We evaluated the effect of overexpressing antioxidant enzymes on the lifespans of transgenic mice that overexpress copper zinc superoxide dismutase (CuZnSOD), catalase, or combinations of either CuZnSOD and catalase or CuZnSOD and manganese superoxide dismutase (MnSOD). Our results show that the overexpression of these major antioxidant enzymes, which are known to scavenge superoxide and hydrogen peroxide in the cytosolic and mitochondrial compartments, is insufficient to extend lifespan in mice.

[1]  D. Gozal,et al.  Manganese superoxide dismutase protects mouse cortical neurons from chronic intermittent hypoxia-mediated oxidative damage , 2007, Neurobiology of Disease.

[2]  Arlan Richardson,et al.  Reduction in glutathione peroxidase 4 increases life span through increased sensitivity to apoptosis. , 2007, The journals of gerontology. Series A, Biological sciences and medical sciences.

[3]  F. Muller,et al.  Trends in oxidative aging theories. , 2007, Free radical biology & medicine.

[4]  J. Vijg,et al.  Characterization of transgenic mice that overexpress both copper zinc superoxide dismutase and catalase. , 2006, Antioxidants & redox signaling.

[5]  M. Emond,et al.  Extension of Murine Life Span by Overexpression of Catalase Targeted to Mitochondria , 2005, Science.

[6]  David B. Allison,et al.  Statistical methods for testing effects on “maximum lifespan” , 2004, Mechanisms of Ageing and Development.

[7]  J. Tower,et al.  Effects of simultaneous over-expression of Cu/ZnSOD and MnSOD on Drosophila melanogaster life span , 2004, Mechanisms of Ageing and Development.

[8]  Arlan Richardson,et al.  Genetic mouse models of extended lifespan , 2003, Experimental Gerontology.

[9]  H. Remmen,et al.  A strategy for the ubiquitous overexpression of human catalase and CuZn superoxide dismutase genes in transgenic mice , 2003, Mechanisms of Ageing and Development.

[10]  J. Tower,et al.  Induced overexpression of mitochondrial Mn-superoxide dismutase extends the life span of adult Drosophila melanogaster. , 2002, Genetics.

[11]  C. Epstein,et al.  Strain-dependent high-level expression of a transgene for manganese superoxide dismutase is associated with growth retardation and decreased fertility. , 2001, Free radical biology & medicine.

[12]  A. Hilliker,et al.  Targeted neuronal gene expression and longevity in Drosophila , 2000, Experimental Gerontology.

[13]  M. Zámocký,et al.  Understanding the structure and function of catalases: clues from molecular evolution and in vitro mutagenesis. , 1999, Progress in biophysics and molecular biology.

[14]  J. Tower,et al.  FLP Recombinase-Mediated Induction of Cu/Zn-Superoxide Dismutase Transgene Expression Can Extend the Life Span of Adult Drosophila melanogaster Flies , 1999, Molecular and Cellular Biology.

[15]  R. S. Sohal,et al.  Extension of life-span by overexpression of superoxide dismutase and catalase in Drosophila melanogaster. , 1994, Science.

[16]  Niels Keiding,et al.  Statistical Models Based on Counting Processes , 1993 .

[17]  C J Epstein,et al.  Ubiquitous overexpression of CuZn superoxide dismutase does not extend life span in mice. , 2000, The journals of gerontology. Series A, Biological sciences and medical sciences.

[18]  S. Holm A Simple Sequentially Rejective Multiple Test Procedure , 1979 .