Department of Animal Physiology-II, Faculty of Biological Sciences, Complutense University of Madrid (UCM), Spain.
Exp Gerontol. 2013 Oct;48(10):1030-42. doi: 10.1016/j.exger.2013.02.021. Epub 2013 Feb 27.
Comparative studies indicate that long-lived mammals have low rates of mitochondrial reactive oxygen species production (mtROSp) and oxidative damage in their mitochondrial DNA (mtDNA). Dietary restriction (DR), around 40%, extends the mean and maximum life span of a wide range of species and lowers mtROSp and oxidative damage to mtDNA, which supports the mitochondrial free radical theory of aging (MFRTA). Regarding the dietary factor responsible for the life extension effect of DR, neither carbohydrate nor lipid restriction seems to modify maximum longevity. However protein restriction (PR) and methionine restriction (at least 80% MetR) increase maximum lifespan in rats and mice. Interestingly, only 7weeks of 40% PR (at least in liver) or 40% MetR (in all the studied organs, heart, brain, liver or kidney) is enough to decrease mtROSp and oxidative damage to mtDNA in rats, whereas neither carbohydrate nor lipid restriction changes these parameters. In addition, old rats also conserve the capacity to respond to 7weeks of 40% MetR with these beneficial changes. Most importantly, 40% MetR, differing from what happens during both 40% DR and 80% MetR, does not decrease growth rate and body size of rats. All the available studies suggest that the decrease in methionine ingestion that occurs during DR is responsible for part of the aging-delaying effect of this intervention likely through the decrease of mtROSp and ensuing DNA damage that it exerts. We conclude that lowering mtROS generation is a conserved mechanism, shared by long-lived species and dietary, protein, and methionine restricted animals, that decreases damage to macromolecules situated near the complex I mtROS generator, especially mtDNA. This would decrease the accumulation rate of somatic mutations in mtDNA and maybe finally also in nuclear DNA.
比较研究表明，长寿哺乳动物的线粒体活性氧物种产生（mtROSp）和线粒体 DNA（mtDNA）的氧化损伤率较低。饮食限制（DR），约 40%，延长了广泛物种的平均和最大寿命，并降低了 mtROSp 和 mtDNA 的氧化损伤，这支持了线粒体自由基衰老理论（MFRTA）。关于负责 DR 延长寿命作用的饮食因素，碳水化合物或脂质限制似乎都不会改变最大寿命。然而，蛋白质限制（PR）和蛋氨酸限制（至少 80%MetR）可延长大鼠和小鼠的最大寿命。有趣的是，仅 7 周的 40%PR（至少在肝脏中）或 40%MetR（在所有研究的器官，心脏、大脑、肝脏或肾脏中）足以降低大鼠 mtROSp 和 mtDNA 的氧化损伤，而碳水化合物或脂质限制都不会改变这些参数。此外，老年大鼠也保留了对 7 周 40%MetR 做出这些有益变化的反应能力。最重要的是，40%MetR 与 40%DR 和 80%MetR 不同，不会降低大鼠的生长速度和体型。所有现有的研究表明，DR 期间蛋氨酸摄入的减少是这种干预延迟衰老作用的部分原因，可能是通过降低 mtROSp 和随之而来的 DNA 损伤来实现的。我们得出结论，降低 mtROS 的产生是一种保守的机制，长寿物种和饮食、蛋白质和蛋氨酸限制的动物都具有这种机制，它可以降低位于 I 型 mtROS 生成器附近的大分子的损伤，尤其是 mtDNA。这将降低 mtDNA 中体细胞突变的积累率，也许最终也会降低核 DNA 中的积累率。
