Parkes T L, Elia A J, Dickinson D, Hilliker A J, Phillips J P, Boulianne G L
Department of Molecular Biology and Genetics, University of Guelph, Ontario, Canada.
Nat Genet. 1998 Jun;19(2):171-4. doi: 10.1038/534.
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.
活性氧（RO）已被确认为衰老和寿命决定中的一个重要效应因子。然而，氧化损伤作用于限制整个生物体寿命的具体细胞类型尚未明确确定。编码氧自由基代谢酶铜锌超氧化物歧化酶（SOD1）的基因突变与在缩短寿命的麻痹性疾病——家族性肌萎缩侧索硬化症（FALS；参考文献4）中发生的脑和脊髓运动神经元丧失之间的关联，表明在运动神经元中特异性发生的慢性且未修复的氧化损伤可能是衰老的一个关键致病因素。为了验证这一假设，我们构建了在成年运动神经元中特异性表达人SOD1的转基因果蝇。我们发现，在单一细胞类型即运动神经元中单一基因SOD1的过表达可使正常寿命延长高达40%，并挽救了寿命较短的Sod基因缺失突变体的寿命。对氧化应激的抗性增强表明，在这些果蝇中观察到的寿命延长是由于RO代谢增强所致。这些结果表明，运动神经元中的SOD活性是果蝇衰老和寿命决定中的一个重要因素。
