Gredilla R, López-Torres M, Barja G
Department of Animal Biology-II, Faculty of Biology, Complutense University, Madrid 28040, Spain.
Microsc Res Tech. 2002 Nov 15;59(4):273-7. doi: 10.1002/jemt.10204.
In the present study, the question if medium-term (4 months) caloric restriction (40%) decreases mitochondrial H2O2 production and oxidative DNA damage was investigated. Caloric restriction (CR) is the only experimental manipulation that increases maximum life span. Previous long-term CR studies have showed that CR decreases the mitochondrial rate of free radical production in diverse tissues and species. Those studies agree with the idea that the superior longevity of the restricted animals can be partly due to their lower mitochondrial rate of free radical generation. However, caloric restriction effects strongly depend on implementation time. Previous studies have shown that the decrease induced by CR on oxygen radical generation and oxidative damage to mitochondrial DNA occurs after 1 year but not after 6 weeks of restriction. In the present investigation, mitochondrial H2O2 production did not change in medium-term (4 months) caloric restricted animals, and, in agreement with that, no differences were found in either mitochondrial or nuclear oxidative DNA damage between restricted and ad libitum-fed animals. These results confirm the importance of the time of CR implementation, and show that time longer than 4 months is needed to decrease the mitochondrial rate of free radical generation and the oxidative damage to mtDNA in the rat heart.
在本研究中，探讨了中期（4个月）热量限制（40%）是否会降低线粒体过氧化氢的产生以及氧化性DNA损伤。热量限制（CR）是唯一能延长最大寿命的实验性操作。先前的长期CR研究表明，CR可降低不同组织和物种中线粒体自由基的产生速率。这些研究支持这样一种观点，即受限动物的超长寿命可能部分归因于其较低的线粒体自由基生成速率。然而，热量限制的效果在很大程度上取决于实施时间。先前的研究表明，CR对氧自由基生成和线粒体DNA氧化损伤的降低作用在限制1年后才会出现，而在限制6周后并未出现。在本研究中，中期（4个月）热量限制的动物线粒体过氧化氢的产生没有变化，与此一致的是，在受限动物和自由采食动物之间，线粒体或核氧化性DNA损伤均未发现差异。这些结果证实了CR实施时间的重要性，并表明需要超过4个月的时间才能降低大鼠心脏线粒体自由基的产生速率以及对线粒体DNA的氧化损伤。
