Department of Biology, McGill University, Montreal, QC, Canada H3A 1B1.
Proc Natl Acad Sci U S A. 2012 Apr 10;109(15):5785-90. doi: 10.1073/pnas.1116158109. Epub 2012 Mar 26.
Reactive oxygen species (ROS) are toxic oxygen-containing molecules that can damage multiple components of the cell and have been proposed to be the primary cause of aging. The antioxidant enzyme superoxide dismutase (SOD) is the only eukaryotic enzyme capable of detoxifying superoxide, one type of ROS. The fact that SOD is present in all aerobic organisms raises the question as to whether SOD is absolutely required for animal life and whether the loss of SOD activity will result in decreased lifespan. Here we use the genetic model organism Caenorhabditis elegans to generate an animal that completely lacks SOD activity (sod-12345 worms). We show that sod-12345 worms are viable and exhibit a normal lifespan, despite markedly increased sensitivity to multiple stresses. This is in stark contrast to what is observed in other genetic model organisms where the loss of a single sod gene can result in severely decreased survival. Investigating the mechanism underlying the normal lifespan of sod-12345 worms reveals that their longevity results from a balance between the prosurvival signaling and the toxicity of superoxide. Overall, our results demonstrate that SOD activity is dispensable for normal animal lifespan but is required to survive acute stresses. Moreover, our findings indicate that maintaining normal stress resistance is not crucial to the rate of aging.
活性氧（ROS）是有毒的含氧分子，可以破坏细胞的多种成分，被认为是衰老的主要原因。抗氧化酶超氧化物歧化酶（SOD）是唯一能够解毒超氧化物的真核酶，超氧化物是 ROS 的一种。SOD 存在于所有需氧生物中，这就提出了一个问题，即 SOD 是否是动物生命所必需的，以及 SOD 活性的丧失是否会导致寿命缩短。在这里，我们使用遗传模式生物秀丽隐杆线虫来生成一种完全缺乏 SOD 活性的动物（sod-12345 线虫）。我们发现，sod-12345 线虫是可行的，并且表现出正常的寿命，尽管对多种应激的敏感性明显增加。这与在其他遗传模式生物中观察到的情况形成鲜明对比，在其他遗传模式生物中，单个 sod 基因的缺失会导致存活率严重下降。研究 sod-12345 线虫正常寿命的机制表明，它们的长寿是由生存信号和超氧化物毒性之间的平衡所决定的。总的来说，我们的结果表明，SOD 活性对于正常动物寿命不是必需的，但对于应对急性应激是必需的。此外，我们的发现表明，维持正常的应激抗性对于衰老速度并不重要。
