老化会伴随着与年龄相关的各种疾病以及身体外貌的变化，而且在不同的人身上有着不同的速度。科学家之前已经将老化归咎于生命中累积的细胞损耗，但是并未考虑可能遗传的老化速度。现在，一个来自瑞典卡罗林斯卡医学院和德国马克斯普朗克生物研究所的研究团队已经发现，线粒体中的受损DNA在一定程度上会控制实验鼠的老化速度。
研究人员声称，遗传自母体的线粒体DNA或许会决定你的老化速度。
马克斯普朗克研究所的研究人员Nils-Göran Larsson说道：“我们之前证实的是线粒体DNA随着动物老化会出现损伤。但是现在，我们也发现一些损伤在出生时就已经存在，而且是从母亲遗传给了孩子。”线粒体DNA与存在于细胞核的DNA不同，它们遗传自双亲，而线粒体DNA只来源于母体基因。Larsson在一份声明中说道，研究人员发现线粒体DNA随着时间出现损伤，细胞的能量制造逐渐变得残缺而且促使老化出现。
为了确定线粒体DNA损伤对老化产生的效果，研究团队饲养了伴有各种不同程度DNA损伤的实验室老鼠，而且通过测量体重、生育能力和红细胞总数等健康条件来估算它们的老化速度。研究团队发现，DNA损伤程度高的老鼠会出现较低的健康水平。然而线粒体DNA损伤与环境压力导致老化之间的相对关系尚不清楚。
Larsson声称：“虽然这些发现有可能暗示着人类的老化速度，但是我们也需要进行额外的研究。我们使用了一系列的实验条件来确定我们的研究结果，而且我们认为它们适用于人类，但是这当然需要通过人类试验进行证实。”研究团队的下一个计划就是研究损伤线粒体DNA在老化中的相对角色，他们将通过基因工程减少突变线粒体DNA的遗传水平。Larsson声称，他们希望他们的研究能够为其它研究人员提供研究的基础。(生物谷 Bioon.com)
生物谷推荐的英文内容
A mother’s genes influence her child’s ageing
As we grow older, not only the function of organs slows down. Also on a cellular level more and more damages occur. One reason is that DNA errors accumulate which cause defective cells. Now a team of researchers lead by Nils-Göran Larsson at the Max Planck Institute for Biology of Ageing in Cologne has shown that ageing is determined not only by the accumulation of DNA damage that occurs during lifetime but also by damage that we acquire from our mothers. In a study on mice, the researchers have shown that mutations of maternally inherited mitochondrial DNA influence the offspring’s ageing process starting from birth.
Ageing is a complex process, in the course of which more and more damage accumulates within the bodies’ tissues, cells and molecules – with serious consequences: Organs lose their function and mortality risk increases. Why some people age faster than others has many reasons that are still unsolved. However, damage that occurs within the mitochondria – the cell’s powerhouses – seems to be of particular importance for ageing.
“The mitochondrion contains its own DNA, the so-called mitochondrial DNA or mtDNA, which changes faster than the DNA in the nucleus, and this has a significant impact on the ageing process,” says Nils-Göran Larsson, Director at the Max Planck Institute for Biology of Ageing in Cologne and scientist at the Karolinska Institute in Stockholm. Together with Lars Olson, also a scientist at the Karolinska Institute, he has led the study.
“Many mutations in the mitochondria gradually disable the cell’s energy production.” Contrary to previous findings, not only mutations that accumulate during lifetime play a role: “Surprisingly, we discovered that our mother’s mitochondrial DNA seems to influence our own ageing,” says James Stewart, a researcher in Larsson’s department. “If mice inherit mtDNA with mutations from their mother, they age more quickly.” Thus, some of the mutations that cause ageing are already present at birth.
In ageing research, mitochondria have been scrutinized by researchers for a long time already. The mitochondria in a cell contain thousand of copies of a circular DNA genome. These encode, for instance, proteins that are important for the enzymes of the respiratory chain. Whereas the DNA within the nucleus comes from both parents, the mitochondrial DNA only includes maternal genes, as mitochondria are transmitted to offspring via the oocyte and not via sperm cells. As the numerous DNA molecules within a cell’s mitochondria mutate independently from each other, normal and damaged mtDNA molecules are passed to the next generation.
To examine which effects mtDNA damage exerts on offspring, researchers used a mouse model. Mice that inherited mutations of mtDNA from their mother not only died quicker compared to those without inherited defects, but also showed premature ageing effects like reduced body mass or a decrease in male’s fertility. Moreover, these rodents were prone to heart muscle disease.
As the researchers discovered, mutations of mtDNA not only can accelerate ageing but also impair development: In mice that, in addition to their inherited defects, accumulated mutations of mtDNA during their lifetime, researchers found disturbances of brain development. They conclude that defects of mtDNA that are inherited and those that are acquired later in life add up and finally reach a critical number.
“Our findings shed light on the ageing process and strongly suggest that the mitochondria play a key role in ageing. They also show that it is important to reduce the number of mutations,” says Larsson. However, the question of whether it is possible to affect the degree of mtDNA damage through, for example, lifestyle intervention is yet to be investigated. In the future, the scientists want to investigate whether a reduced number of mutations can actually increase lifespan in model organisms such as fruit flies and mice.
