sod, motor neurons and drosophila longevity

From: Doug Skrecky (
Date: Wed Mar 08 2000 - 19:12:23 MST

Citations: 1-3
  Mockett RJ. Orr WC. Rahmandar JJ. Benes JJ. Radyuk SN. Klichko VI.
  Sohal RS.
  Department of Biological Sciences, Southern Methodist University, Dallas,
  Texas 75275, USA.
  Overexpression of Mn-containing superoxide dismutase in transgenic
  Drosophila melanogaster.
  Archives of Biochemistry & Biophysics. 371(2):260-9, 1999 Nov 15.
  The general objective of this study was to examine the role of mitochondria
  in the aging process. Two alternative hypotheses were tested: (i) that
  overexpression of Mn superoxide dismutase (Mn SOD) in the mitochondria of
  Drosophila melanogaster would slow the accrual of oxidative
  damage and prolong survival or (ii) that there is an evolved optimum level of
  superoxide anion radical, such that overexpression of Mn SOD would have
  deleterious or neutral effects. Microinjection and mobilization of a
  transgene, which contained a 9-kb genomic sequence encoding Mn SOD, produced
  15 experimental lines overexpressing Mn SOD by 5-116% relative to the
  parental y w strain. Comparisons between these lines and control lines
  containing inserted vector sequences alone indicated that the mean
  longevity of the experimental lines was decreased by 4-5%
  relative to controls. There were no compensatory changes in the metabolic
  rate, level of physical activity, or the levels of other antioxidants, namely
  Cu-Zn SOD, catalase, and glutathione. There were no differences between
  groups in rates of mitochondrial hydrogen peroxide release, protein oxidative
  damage, or resistance to 100% oxygen or starvation conditions. The
  experimental lines had a marginally increased resistance to moderate heat
  stress. These results are consistent with the existence of an optimum level
  of Mn SOD activity which minimizes oxidative stress. The naturally evolved
  level of Mn SOD activity in Drosophila appears to be near
  the optimum required under normal conditions, although the optimum may be
  shifted to a higher level under more stressful conditions. Copyright 1999
  Academic Press.

  Hari R. Burde V. Arking R.
  Department of Biological Sciences, Wayne State University, Detroit, Michigan
  48202, USA.
  Immunological confirmation of elevated levels of CuZn superoxide dismutase
  protein in an artificially selected long-lived strain of
  Drosophila melanogaster.
  Experimental Gerontology. 33(3):227-37, 1998 May.
  Oxidative stress-induced damage is a major causal factor leading to the loss
  of function characteristic of the aging process. Various antioxidant defenses
  are marshalled by the organism so as to combat this oxidative damage and
  delay the onset of senscence. CuZnSOD is one of the major antioxidant enzymes
  and has been shown to play an important role in the extended
  longevity of Drosophila melanogaster.
  Although assays exist with which to measure the CuZnSOD RNA prevalence and
  enzyme activity, there existed no antibodies that permitted the measurement
  of the actual amount of Drosophila enzyme protein present.
  Development of such a tool would enhance our ability to understand mechanisms
  of antioxidant gene expression in this organism. We have developed a
  polyclonal antibody against synthetic SOD peptides that is specific for
  Drosophila CuZnSOD as shown by Western blots. It is very
  sensitive when tested against native Drosophila CuZnSOD
  protein. Its use in our experimental system confirms the prior RNA and enzyme
  activity measurements that indicate that our genetically selected long-lived
  strain has significantly higher levels of CuZnSOD protein than does the
  appropriate control strain.

  Parkes TL. Elia AJ. Dickinson D. Hilliker AJ. Phillips JP. Boulianne GL.
  Department of Molecular Biology and Genetics, University of Guelph, Ontario,
  Extension of Drosophila lifespan by overexpression of human
  SOD1 in motorneurons [comment] [see comments].
  Comment on: Nat Genet 1998 Jun;19(2):105-6, Comment in: Nat Genet 1998
  Jun;19(2):103, 104
  Nature Genetics. 19(2):171-4, 1998 Jun.
  Reactive oxygen (RO) has been identified as an important effector in ageing
  and lifespan determination. The specific cell types, however, in which
  oxidative damage acts to limit lifespan of the whole organism have not been
  explicitly identified. The association between mutations in the gene encoding
  the oxygen radical metabolizing enzyme CuZn superoxide dismutase (SOD1) and
  loss of motorneurons in the brain and spinal cord that occurs in the
  life-shortening paralytic disease, Familial Amyotrophic Lateral Sclerosis
  (FALS; ref. 4), suggests that chronic and unrepaired oxidative damage
  occurring specifically in motor neurons could be a critical causative factor
  in ageing. To test this hypothesis, we generated transgenic
  Drosophila which express human SOD1 specifically in adult
  motorneurons. We show that overexpression of a single gene, SOD1, in a single
  cell type, the motorneuron, extends normal lifespan by up to 40% and rescues
  the lifespan of a short-lived Sod null mutant. Elevated resistance to
  oxidative stress suggests that the lifespan extension observed in these flies
  is due to enhanced RO metabolism. These results show that SOD activity in
  motorneurons is an important factor in ageing and lifespan determination in

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