EXTENSION OF DROSOPHILA LIFE-SPAN BY OVEREXPRESSION OF HUMAN SOD1 IN MOTOR-NEURONS

Reactive oxygen (RO) has been identified as an important effector in a geing and lifespan determination(1-3). The specific cell types, howeve r, in which oxidative damage acts to limit lifespan of the whole organ ism have not been explicitly identified. The association between mutat ions 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, Fami lial Amyotrophic Lateral Sclerosis (FALS; ref. 4), suggests that chron ic and unrepaired oxidative damage occurring specifically in motor neu rons could be a critical causative factor in ageing. To test this hypo thesis, we generated transgenic Drosophila which express human SOD1 sp ecifically in adult motorneurons. We show that overexpression of a sin gle 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 n ull mutant. Elevated resistance to oxidative stress suggests that the lifespan extension observed in these flies is due to enhanced RO metab olism. These results show that SOD activity in motorneurons is an impo rtant factor in ageing and lifespan determination in Drosophila.