带有MCLK1缺陷型线粒体蛋白质的小鼠在年轻阶段会产生更多的活性氧；本周JBC发表的一项研究表明，这类小鼠与正常小鼠相比，其衰老速度较慢且寿命更长，但这种小鼠仍存在生命危险。
线粒体氧应激是解释衰老过程的一种常规理论，线粒体利用再激活氧的方法产生能量，随着时间的流逝，这些氧在体内逐渐积累并开始破坏细胞，包括线粒体本身。近期有几项研究开始质疑这个理论。为了找到更为直接的答案，麦吉尔大学的Siegfried Hekimi及其同事检测了MCLK1缺陷型小鼠的线粒体，这种小鼠具有寿命长的特征。
他们发现，在幼年（3月龄）MCLK1缺陷型小鼠中，其线粒体产能不足而且会生成许多有害的氧自由基；但是令人惊讶的是，当这些小鼠达到23月龄后，它们的线粒体比正常小鼠的功能更好。所以，尽管存在氧应激反应，这类小鼠比正常小鼠受到的衰老恶化作用更少。
为了确定MCLK1缺陷是否在某些方面有保护作用，研究者们将MCLK1缺陷型小鼠与SOD2缺乏症小鼠杂交，SOD2是一种主要的蛋白质抗氧化剂。正常情况下，SOD2缺陷型小鼠细胞内损伤积累的非常，但杂交后，它们表现出损伤程度降低而且出现氧应激反应。
在对这种假说的解释中，Hekimi及其同事认为由于MCLK1缺陷型小鼠的线粒体能够产生很多氧自由基，这种产能低下造成细胞其他组分中产生的能量和氧自由基都有所减少。尽管这样的小鼠在幼年时可能会有更高的患病风险，但是随着年龄增长，它们体内积累的有害物质却比正常小鼠少——该发现有可能说明线粒体应激理论不完全正确。（生物谷Bioon.com）
生物谷推荐原始出处：
J. Biol. Chem., Vol. 284, Issue 30, 20364-20374, July 24, 2009
Reversal of the Mitochondrial Phenotype and Slow Development of Oxidative Biomarkers of Aging in Long-lived Mclk1+/– Mice*
Jérôme Lapointe, Zaruhi Stepanyan, Eve Bigras, and Siegfried Hekimi1
From the From the Department of Biology, McGill University, Montreal, Quebec H3A 1B1, Canada
ABSTRACT
Although there is a consensus that mitochondrial function is somehow linked to the aging process, the exact role played bymitochondria in this process remains unresolved. The discovery that reduced activity of the mitochondrial enzyme CLK-1/MCLK1(also known as COQ7) extends lifespan in both Caenorhabditis elegans and mice has provided a genetic model to test mitochondrial theories of aging. We have recently shown that the mitochondria of young, long-lived, Mclk1+/– mice are dysfunctional, exhibiting reduced energy metabolism and a substantial increase in oxidative stress. Here we demonstrate that this altered mitochondrial condition in young animals paradoxically results in an almost complete protection from the age-de pend ent loss of mitochondrial function as well as in a significant attenuation of the rate of development of oxidative biomarkers of aging. Moreover, we show that reduction in MCLK1 levels can also gradually prevent the deterioration of mitochondrial function and associated increase of global oxidative stress that is normally observed in Sod2+/– mutants. We hypothesize that the mitochondrial dysfunction observed in young Mclk1+/– mutants induces a physiological state that ultimately allows for their slow rate of aging. Thus, our study provides for a unique vertebrate model in which an initialalteration in a specific mitochondrial function is linked to long term beneficial effects on biomarkers of aging and, furthermore, provides for new evidence which indicates that mitochondrial oxidative stress is not causal to aging.
