本文研究为揭示不同个体间的生理学差异提供了新的思路，也为深入研究常见老化相关的疾病，比如糖尿病、心血管疾病及癌症等提供了一定的研究方法。人类机体中有超过2万个基因，单在线粒体中就存在37个基因，同细胞核一样，不管在小鼠还是在人类机体中，线粒体基因组也会表现出一定程度的遗传改变。

研究者发现，非致病性的线粒体DNA突变体对有机体的代谢和老化有着不同的影响，本文研究发现，一系列基因的改变或许可以帮助确定是否我们会经历健康老龄化过程，相关的研究结果也可以帮助我们理解机体老化过程的发生机制。研究者Ana Latorre-Pellicer说道，进行这项研究的关键就是理解基因组、细胞核及线粒体间的组合及相互作用如何诱发机体中细胞适应性的出现。

利用动物模型进行研究，研究者就得到了足够的证据表明，幼年动物机体细胞线粒体DNA的改变就会诱发一系列适应性的细胞机制出现，而这就可以确保机体 进行一种较为健康的老龄化过程。如果我们可以理解健康老龄化背后的生物学机制，我们或许就可以在老龄化期间及时维持长期的机体健康。

线粒体捐赠技术可以潜在抑制促疾病的线粒体DNA的传播，这种治疗方法旨在避免遗传病理性的突变在人群间的传播，该方法包括利用健康供体机体的线粒体 来替换次优的母源性线粒体，然而随着这种新型技术的利用就会产生越来越多的“三父母婴儿”，而这在英国是允许的，而研究者需要对线粒体DNA变异对机体的 影响进行全面的理解。

这项研究强调了供体线粒体DNA的重要性，因为线粒体的捐赠步骤是同受体核基因组适当匹配的一个复杂过程，而研究者也强调了进行线粒体捐赠不可忽视的 一些潜在风险；这就像器官移植和血液移植一样，选择合适的线粒体供体非常重要，因为这可以确保新生的线粒体DNA在遗传性上同母体的线粒体DNA相似。

doi:10.1038/nature18618

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Mitochondrial and nuclear DNA matching shapes metabolism and healthy ageing

Ana Latorre-Pellicer, Raquel Moreno-Loshuertos, Ana Victoria Lechuga-Vieco, Fátima Sánchez-Cabo, Carlos Torroja, Rebeca Acín-Pérez, Enrique Calvo, Esther Aix, Andrés González-Guerra, Angela Logan, María Luisa Bernad-Miana, Eduardo Romanos, Raquel Cruz, Sara Cogliati, Beatriz Sobrino, ángel Carracedo, Acisclo Pérez-Martos, Patricio Fernández-Silva, Jesús Ruíz-Cabello, Michael P. Murphy, Ignacio Flores, Jesús Vázquez &José Antonio Enríquez

Human mitochondrial DNA (mtDNA) shows extensive within-population sequence variability1. Many studies suggest that mtDNA variants may be associated with ageing or diseases2, 3, 4, although mechanistic evidence at the molecular level is lacking5, 6. Mitochondrial replacement has the potential to prevent transmission of disease-causing oocyte mtDNA. However, extension of this technology requires a comprehensive understanding of the physiological relevance of mtDNA sequence variability and its match with the nuclear-encoded mitochondrial genes. Studies in conplastic animals7, 8, 9 allow comparison of individuals with the same nuclear genome but different mtDNA variants, and have provided both supporting and refuting evidence that mtDNA variation influences organismal physiology. However, most of these studies did not confirm the conplastic status, focused on younger animals, and did not investigate the full range of physiological and phenotypic variability likely to be influenced by mitochondria. Here we systematically characterized conplastic mice throughout their lifespan using transcriptomic, proteomic, metabolomic, biochemical, physiological and phenotyping studies. We show that mtDNA haplotype profoundly influences mitochondrial proteostasis and reactive oxygen species generation, insulin signalling, obesity, and ageing parameters including telomere shortening and mitochondrial dysfunction, resulting in profound differences in health longevity between conplastic strains.