Extension of Drosophila lifespan by overexpression of human SOD1 in motorneurons.

Authors: Parkes TL; Elia AJ; Dickinson D; Hilliker AJ; Phillips JP; Boulianne GL

Abstract: 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.

Keywords: Aging/genetics/physiology; Animals; Drosophila; Genotype; Humans; *Longevity/genetics/physiology; Motor Neurons/*enzymology/physiology; Oxidative Stress/genetics/physiology; Reactive Oxygen Species; Superoxide Dismutase/biosynthesis/genetics/*physiology; Transfection
Journal: Nature genetics
Volume: 19
Issue: 2
Pages: 171-4
Date: June 10, 1998
PMID: 9620775
Select reference article to upload


Citation:

Parkes TL, Elia AJ, Dickinson D, Hilliker AJ, Phillips JP, Boulianne GL (1998) Extension of Drosophila lifespan by overexpression of human SOD1 in motorneurons. Nature genetics 19: 171-4.


Study
Update (Admin) | Auto-Update

Comment on This Data Unit