Extension of Drosophila lifespan by overexpression of human SOD1 in motorneurons.
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 Drosophila.
Parkes
T L
TL
Department of Molecular Biology and Genetics, University of Guelph, Ontario, Canada.
Elia
A J
AJ
Dickinson
D
D
Hilliker
A J
AJ
Phillips
J P
JP
Boulianne
G L
GL
D000375:Aging / Q000235:genetics / Q000502:physiology; D000818:Animals; D004330:Drosophila; D005838:Genotype; D006801:Humans; D008136:Longevity / Q000235:genetics / Q000502:physiology; D009046:Motor Neurons / Q000201:enzymology* / Q000502:physiology; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000072105:Superoxide Dismutase-1; D014162:Transfection
D017382:Reactive Oxygen Species; C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1