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Extension of Drosophila lifespan by overexpression of human SOD1 in motorneurons

Nature Genetics volume 19, pages 171–174 (1998)Cite this article

Abstract

Reactive oxygen (RO) has been identified as an important effector in ageing and lifespan determination1,2,3. 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 Drosophila.

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Figure 1: GAL4-activated expression of human SOD1 in motorneurons.
Figure 2: Detection of SOD1 protein.
Figure 3: Extension of normal adult lifespan by expression of SOD1 in motorneurons.
Figure 4: Restoration of adult lifespan in Sod null mutant by SOD1 expression in motorneurons.
Figure 5: Motorneuronal SOD and lifespan in Drosophila.
Figure 6: Expression of SOD1 in motorneurons confers resistance to oxidative stress in Sod null mutants.

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Acknowledgements

We thank K. Kirby for the SOD-activity assays and for many helpful discussions; P. St. George–Hyslop for the human SOD1 cDNA, A. Campos and R. Jacobs for consultation on the in situ hybridization data and W.S. Trimble for critical reading of the manuscript. Supported by grants from the Medical Research Council of Canada (G.L.B., A.J.H., J.P.P.) and The Natural Sciences and Engineering Research Council of Canada (A.J.H., J.P.P.).

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Author notes

  1. Andrew J. Elia and Gabrielle L. Boulianne: The Research Institute & Program in Developmental Biology, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8 Departments of Molecular and Medical Genetics & Zoology, University of Toronto, Toronto, Ontario, Canada. T.L.P. & A.J.E. contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular Biology and Genetics, University of Guelph, Guelph, N1G 2W1, Ontario, Canada

    Tony L. Parkes, Dale Dickinson, Arthur J. Hilliker & John P. Phillips

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  1. Tony L. Parkes
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  2. Andrew J. Elia
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  4. Arthur J. Hilliker
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Correspondence to John P. Phillips.

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Parkes, T., Elia, A., Dickinson, D. et al. Extension of Drosophila lifespan by overexpression of human SOD1 in motorneurons. Nat Genet 19, 171–174 (1998). https://doi.org/10.1038/534

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