線粒體是細胞中的發(fā)電廠——能量產(chǎn)生單元,。以前的研究發(fā)現(xiàn),，在人和小鼠體內(nèi),，線粒體點變異在老化過程中積累,。如今，研究人員在本周在線出版的《自然—遺傳學(xué)》中報道說,，小鼠體內(nèi)大量的線粒體點變異與其老化過程沒有直接關(guān)系,，新發(fā)現(xiàn)與“線粒體點變異是老化過程誘導(dǎo)因素”的傳統(tǒng)觀點相矛盾。
死亡原理中的線粒體理論是一個頗有爭議的理論,，這個理論認為,，與生命期相當(dāng)?shù)木€粒體DNA變異與衰老過程中觀察到的組織功能衰落有關(guān)。Lawrence Loeb和同事使用一種全新的,、高度敏感的方法來確定在小鼠的正常老化過程中,，線粒體DNA中以單個堿基對為基礎(chǔ)的變異速度，以及在線粒體變異小鼠體內(nèi)線粒體的點變異速度,。線粒體變異小鼠線粒體點變異量是正常小鼠的500倍,。
研究人員發(fā)現(xiàn)，隨著年齡的增長,，正常小鼠的線粒體點變異增加了11倍,，而線粒體變異小鼠卻沒有表現(xiàn)出隨著年齡增長的明顯特征,。
特別需要指出的是，新研究并沒有排除線粒體DNA的大量剔除與老化的關(guān)系,。比如,，以前的研究顯示，線粒體DNA中的大量剔除與老年人和帕金森氏癥患者的某種神經(jīng)元損害有關(guān),。
部分英文原文：
Published online: 4 March 2007; | doi:10.1038/ng1988
Mitochondrial point mutations do not limit the natural lifespan of mice
Marc Vermulst1, Jason H Bielas1, Gregory C Kujoth2, Warren C Ladiges3, Peter S Rabinovitch1, Tomas A Prolla2 & Lawrence A Loeb1
1 Department of Pathology, University of Washington, Seattle, Washington 91895, USA.
2 Departments of Genetics and Medical Genetics, University of Wisconsin, Madison, Wisconsin 53706, USA.
3 Department of Comparative Medicine, University of Washington, Seattle, Washington 98195, USA.
Correspondence should be addressed to Lawrence A Loeb [email protected]
Whether mitochondrial mutations cause mammalian aging, or are merely correlated with it, is an area of intense debate1. Here, we use a new, highly sensitive assay2 to redefine the relationship between mitochondrial mutations and age. We measured the in vivo rate of change of the mitochondrial genome at a single–base pair level in mice, and we demonstrate that the mutation frequency in mouse mitochondria is more than ten times lower than previously reported. Although we observed an 11-fold increase in mitochondrial point mutations with age, we report that a mitochondrial mutator mouse3 was able to sustain a 500-fold higher mutation burden than normal mice, without any obvious features of rapidly accelerated aging. Thus, our results strongly indicate that mitochondrial mutations do not limit the lifespan of wild-type mice.
