Extension of Drosophila lifespan by overexpression of human SOD1 in motorneurons
Extension of Drosophila lifespan by overexpression of human SOD1 in motorneurons
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DOI：
10.1038/534
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发表时间：
1998-06-01
期刊：
影响因子：
30.8
通讯作者：
Boulianne, GL
中科院分区：
文献类型：
--
作者：
Parkes, TL;Elia, AJ;Boulianne, GL
活性氧(RO)已被认为是衰老和寿命决定的重要影响因素(1-3)。然而，氧化损伤限制整个生物体寿命的具体细胞类型尚未明确确定。氧自由基代谢酶CuZN超氧化物歧化酶(SOD1)编码基因突变与脑和脊髓运动神经元丢失之间的关系发生在缩短寿命的瘫痪疾病家族性肌萎缩侧索硬化症(FALS)中。4)，这表明专门发生在运动神经元中的慢性和未修复的氧化损伤可能是衰老的一个关键因素。为了验证这一假设，我们创造了转基因果蝇，它在成年运动神经元中特异性地表达人SOD1。我们发现，在单细胞类型运动神经元中过表达单一基因SOD1，可以将正常寿命延长高达40%，并挽救短暂的SOD缺失突变体的寿命。提高对氧化应激的抵抗力表明，在这些果蝇中观察到的寿命延长是由于RO代谢的增强。这些结果表明，运动神经元中的超氧化物歧化酶活性是决定果蝇衰老和寿命的重要因素。
Reactive oxygen (RO) has been identified as an important effector in ageing and lifespan determination(1-3). 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.