Lambert Adrian J, Boysen Helen M, Buckingham Julie A, Yang Ting, Podlutsky Andrej, Austad Steven N, Kunz Thomas H, Buffenstein Rochelle, Brand Martin D
Medical Research Council, Dunn Human Nutrition Unit, Hills Road, Cambridge CB2 2XY, UK.
Aging Cell. 2007 Oct;6(5):607-18. doi: 10.1111/j.1474-9726.2007.00312.x. Epub 2007 Jun 27.
An inverse correlation between free radical production by isolated mitochondria and longevity in homeotherms has been reported, but previous comparative studies ignored possible confounding effects of body mass and phylogeny. We investigated this correlation by comparing rates of hydrogen peroxide (H(2)O(2)) production by heart mitochondria isolated from groups or pairs of species selected to have very different maximum lifespans but similar body masses (small mammals, medium-sized mammals, birds). During succinate oxidation, H(2)O(2) production rates were generally lower in the longer-lived species; the differences arose at complex I of the electron transport chain during reverse electron transport. Additional data were obtained from large species and the final dataset comprised mouse, rat, white-footed mouse, naked mole-rat, Damara mole-rat, guinea pig, baboon, little brown bat, Brazilian free-tailed bat, ox, pigeon and quail. In this dataset, maximum lifespan was negatively correlated with H(2)O(2) production at complex I during reverse electron transport. Analysis of residual maximum lifespan and residual H(2)O(2) production revealed that this correlation was even more significant after correction for effects of body mass. To remove effects of phylogeny, independent phylogenetic contrasts were obtained from the residuals. These revealed an inverse association between maximum lifespan and H(2)O(2) production that was significant by sign test, but fell short of significance by regression analysis. These findings indicate that enhanced longevity may be causally associated with low free radical production by mitochondria across species over two classes of vertebrate homeotherms.
据报道，恒温动物中分离出线粒体产生自由基的量与寿命之间存在负相关，但以往的比较研究忽略了体重和系统发育可能产生的混杂效应。我们通过比较从选定的具有非常不同的最大寿命但体重相似的物种组或物种对（小型哺乳动物、中型哺乳动物、鸟类）中分离出的心脏线粒体产生过氧化氢（H₂O₂）的速率，来研究这种相关性。在琥珀酸氧化过程中，寿命较长的物种中H₂O₂的产生速率通常较低；这些差异出现在电子传递链复合体I的逆向电子传递过程中。我们还从大型物种中获得了额外的数据，最终数据集包括小鼠、大鼠、白足鼠、裸鼹鼠、达马拉鼹鼠、豚鼠、狒狒、小棕蝠、巴西无尾蝠、牛、鸽子和鹌鹑。在这个数据集中，最大寿命与逆向电子传递过程中复合体I处H₂O₂的产生呈负相关。对剩余最大寿命和剩余H₂O₂产生量的分析表明，在校正体重影响后，这种相关性更加显著。为了消除系统发育的影响，我们从残差中获得了独立的系统发育对比。这些结果显示，最大寿命与H₂O₂产生之间存在负相关，通过符号检验具有显著性，但通过回归分析未达到显著性。这些发现表明，在两类脊椎动物恒温动物中，寿命延长可能与线粒体产生低自由基量存在因果关系。
