sod,motor neurons and drosophila longevity
oberon at vcn.bc.ca
Wed Mar 8 21:27:32 EST 2000
Mockett RJ. Orr WC. Rahmandar JJ. Benes JJ. Radyuk SN. Klichko VI.
Department of Biological Sciences, Southern Methodist University, Dallas,
Texas 75275, USA.
Overexpression of Mn-containing superoxide dismutase in transgenic
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
Hari R. Burde V. Arking R.
Department of Biological Sciences, Wayne State University, Detroit, Michigan
Immunological confirmation of elevated levels of CuZn superoxide dismutase
protein in an artificially selected long-lived strain of
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
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
More information about the Ageing