Tranah Gregory J, Yaffe Kristine, Katzman Shana M, Lam Ernest T, Pawlikowska Ludmila, Kwok Pui-Yan, Schork Nicholas J, Manini Todd M, Kritchevsky Stephen, Thomas Fridtjof, Newman Anne B, Harris Tamara B, Coleman Anne L, Gorin Michael B, Helzner Elizabeth P, Rowbotham Michael C, Browner Warren S, Cummings Steven R
California Pacific Medical Center Research Institute, San Francisco.
Department of Psychiatry, Department of Neurology and Department of Epidemiology, University of California San Francisco and the San Francisco VA Medical Center.
J Gerontol A Biol Sci Med Sci. 2015 Nov;70(11):1418-24. doi: 10.1093/gerona/glv097. Epub 2015 Aug 31.
Mitochondrial DNA (mtDNA) heteroplasmy is a mixture of normal and mutated mtDNA molecules in a cell. High levels of heteroplasmy at specific mtDNA sites lead to inherited mitochondrial diseases with neurological, sensory, and movement impairments. Here we test the hypothesis that heteroplasmy levels in elderly adults are associated with impaired function resembling mild forms of mitochondrial disease.
We examined platelet mtDNA heteroplasmy at 20 disease-causing sites for associations with neurosensory and mobility function among 137 participants from the community-based Health, Aging, and Body Composition Study.
Elevated mtDNA heteroplasmy at four mtDNA sites in complex I and tRNA genes was nominally associated with reduced cognition, vision, hearing, and mobility: m.10158T>C with Modified Mini-Mental State Examination score (p = .009); m.11778G>A with contrast sensitivity (p = .02); m.7445A>G with high-frequency hearing (p = .047); and m.5703G>A with 400 m walking speed (p = .007).
These results indicate that increased mtDNA heteroplasmy at disease-causing sites is associated with neurosensory and mobility function in older persons. We propose the novel use of mtDNA heteroplasmy as a simple, noninvasive predictor of age-related neurologic, sensory, and movement impairments.
线粒体DNA(mtDNA)异质性是指细胞中正常和突变的mtDNA分子的混合物。特定mtDNA位点的高异质性水平会导致遗传性线粒体疾病,并伴有神经、感官和运动功能障碍。在此,我们检验这样一个假设,即老年人的异质性水平与类似于轻度线粒体疾病形式的功能受损有关。
我们在基于社区的健康、衰老和身体成分研究的137名参与者中,检测了20个致病位点的血小板mtDNA异质性,以探讨其与神经感觉和运动功能的关联。
复合体I和tRNA基因中四个mtDNA位点的mtDNA异质性升高,名义上与认知、视力、听力和运动功能下降相关:m.10158T>C与改良简易精神状态检查表评分相关(p = 0.009);m.11778G>A与对比敏感度相关(p = 0.02);m.7445A>G与高频听力相关(p = 0.047);m.5703G>A与400米步行速度相关(p = 0.007)。
这些结果表明,致病位点处mtDNA异质性增加与老年人的神经感觉和运动功能相关。我们提出将mtDNA异质性作为一种简单、无创的预测与年龄相关的神经、感官和运动功能障碍的新方法。