Decreased Energy Metabolism Extends Life Span in Caenorhabditis elegans Without Reducing Oxidative Damage
Decreased Energy Metabolism Extends Life Span in Caenorhabditis elegans Without Reducing Oxidative Damage
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DOI：
10.1534/genetics.110.115378
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发表时间：
2010-06
期刊：
影响因子：
3.3
通讯作者：
J. V. Van Raamsdonk;Y. Meng;Darius Camp;Wen Yang;Xihua Jia;C. Bénard;S. Hekimi
中科院分区：
文献类型：
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作者：
J. V. Van Raamsdonk;Y. Meng;Darius Camp;Wen Yang;Xihua Jia;C. Bénard;S. Hekimi
基于自由基和衰老的生存率理论，已经提出代谢减少通过减少活性氧（ROS）的产生而导致寿命增加。在这篇文章中，我们研究线粒体能量代谢和寿命之间的关系，通过使用Clk突变体在秀丽隐杆线虫。Clk突变体的特征在于缓慢的生理速率、延迟的发育和增加的寿命。这种表型表明，寿命的延长可以通过减少能量消耗来实现。为了验证这一假设，我们确定了六个新的Clk突变体在屏幕上的蠕虫，排便缓慢，发育缓慢，可以从母体中获救。有趣的是，所有11个Clk突变体都增加了寿命，尽管缓慢的生理速率被用作唯一的筛选标准。尽管Clk突变体中线粒体功能降低，但ATP水平正常或升高，表明能量利用降低。为了确定Clk突变体的寿命是否是由于ROS产生减少，我们检查了对氧化应激和氧化损伤的敏感性。我们发现没有证据表明，尽管正常或升高水平的超氧化物歧化酶的Clk突变体的抗氧化应激或减少氧化损伤的系统性增加。总的来说，我们的研究结果表明，降低能量代谢可以导致寿命延长，而不会减少ROS的产生。
On the basis of the free radical and rate of living theories of aging, it has been proposed that decreased metabolism leads to increased longevity through a decreased production of reactive oxygen species (ROS). In this article, we examine the relationship between mitochondrial energy metabolism and life span by using the Clk mutants in Caenorhabditis elegans. Clk mutants are characterized by slow physiologic rates, delayed development, and increased life span. This phenotype suggests that increased life span may be achieved by decreasing energy expenditure. To test this hypothesis, we identified six novel Clk mutants in a screen for worms that have slow defecation and slow development and that can be maternally rescued. Interestingly, all 11 Clk mutants have increased life span despite the fact that slow physiologic rates were used as the only screening criterion. Although mitochondrial function is decreased in the Clk mutants, ATP levels are normal or increased, suggesting decreased energy utilization. To determine whether the longevity of the Clk mutants results from decreased production of ROS, we examined sensitivity to oxidative stress and oxidative damage. We found no evidence for systematically increased resistance to oxidative stress or decreased oxidative damage in the Clk mutants despite normal or elevated levels of superoxide dismutases. Overall, our findings suggest that decreased energy metabolism can lead to increased life span without decreased production of ROS.