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), suggests that chronic and unrepaired oxidative
damage occuring specifically in motor neurons could be a critical factor in
ageing. To test this hypothesis, we generated transgenetic Drosophilia
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
Drosophilia.