Guo Xinhong, Kudryavtseva Elena, Bodyak Natalya, Nicholas Alexander, Dombrovsky Igor, Yang Deye, Kraytsberg Yevgenya, Simon David K, Khrapko Konstantin
Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA, USA.
Biochim Biophys Acta. 2010 Jun-Jul;1797(6-7):1159-62. doi: 10.1016/j.bbabio.2010.04.005. Epub 2010 Apr 11.
Mitochondrial DNA (mtDNA) deletions have been reported to accumulate to high levels in substantia nigra of older humans, and these mutations are suspected of causing age-related degeneration in this area. We have compared levels of mtDNA deletions in humans and mice and report here that levels of deletions in the mouse are very significantly lower than in humans. While human mtDNA from substantia nigra contained more than 5% of deleted molecules, mouse substantia nigra contained less than 0.5%. These results imply that mtDNA deletions are unlikely to play any significant role in of murine substantia nigra aging and further call for caution in using mouse models in studies of the role of mtDNA deletions in aging and neurodegeneration. On a more general note, these results support the view that critical targets of the various aging processes may differ significantly between distant species.
据报道,线粒体DNA(mtDNA)缺失在老年人黑质中积累到很高水平,并且这些突变被怀疑导致该区域与年龄相关的退化。我们比较了人类和小鼠中mtDNA缺失的水平,并在此报告,小鼠中的缺失水平显著低于人类。来自黑质的人类mtDNA含有超过5%的缺失分子,而小鼠黑质中则少于0.5%。这些结果表明,mtDNA缺失不太可能在小鼠黑质衰老中起任何重要作用,并进一步呼吁在研究mtDNA缺失在衰老和神经退行性变中的作用时,谨慎使用小鼠模型。更一般地说,这些结果支持这样一种观点,即不同物种之间各种衰老过程的关键靶点可能存在显著差异。