帶有MCLK1缺陷型線(xiàn)粒體蛋白質(zhì)的小鼠在年輕階段會(huì)產(chǎn)生更多的活性氧；本周JBC發(fā)表的一項(xiàng)研究表明,，這類(lèi)小鼠與正常小鼠相比，其衰老速度較慢且壽命更長(zhǎng),，但這種小鼠仍存在生命危險(xiǎn),。
線(xiàn)粒體氧應(yīng)激是解釋衰老過(guò)程的一種常規(guī)理論，線(xiàn)粒體利用再激活氧的方法產(chǎn)生能量,，隨著時(shí)間的流逝，這些氧在體內(nèi)逐漸積累并開(kāi)始破壞細(xì)胞，包括線(xiàn)粒體本身,。近期有幾項(xiàng)研究開(kāi)始質(zhì)疑這個(gè)理論,。為了找到更為直接的答案，麥吉爾大學(xué)的Siegfried Hekimi及其同事檢測(cè)了MCLK1缺陷型小鼠的線(xiàn)粒體,，這種小鼠具有壽命長(zhǎng)的特征,。
他們發(fā)現(xiàn)，在幼年（3月齡）MCLK1缺陷型小鼠中,，其線(xiàn)粒體產(chǎn)能不足而且會(huì)生成許多有害的氧自由基,；但是令人驚訝的是，當(dāng)這些小鼠達(dá)到23月齡后,，它們的線(xiàn)粒體比正常小鼠的功能更好,。所以，盡管存在氧應(yīng)激反應(yīng),，這類(lèi)小鼠比正常小鼠受到的衰老惡化作用更少,。
為了確定MCLK1缺陷是否在某些方面有保護(hù)作用，研究者們將MCLK1缺陷型小鼠與SOD2缺乏癥小鼠雜交,，SOD2是一種主要的蛋白質(zhì)抗氧化劑,。正常情況下，SOD2缺陷型小鼠細(xì)胞內(nèi)損傷積累的非常,，但雜交后,，它們表現(xiàn)出損傷程度降低而且出現(xiàn)氧應(yīng)激反應(yīng)。
在對(duì)這種假說(shuō)的解釋中,，Hekimi及其同事認(rèn)為由于MCLK1缺陷型小鼠的線(xiàn)粒體能夠產(chǎn)生很多氧自由基,，這種產(chǎn)能低下造成細(xì)胞其他組分中產(chǎn)生的能量和氧自由基都有所減少。盡管這樣的小鼠在幼年時(shí)可能會(huì)有更高的患病風(fēng)險(xiǎn),，但是隨著年齡增長(zhǎng),，它們體內(nèi)積累的有害物質(zhì)卻比正常小鼠少——該發(fā)現(xiàn)有可能說(shuō)明線(xiàn)粒體應(yīng)激理論不完全正確,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
