裸鼹鼠挑战对衰老和繁殖的传统认知

Naked mole-rats defy conventions of aging and reproduction
裸鼹鼠挑战对衰老和繁殖的传统认知

Naked mole-rats live in colonies of two breeders and around 300 non-breeding workers. Although the breeding pair carries the metabolic cost of reproduction and, in the queen’s case, lactation, they live longer than non-breeders and remain fertile throughout their lives. Researchers at the Leibniz Institute on Aging in Germany investigated the genetic mechanisms beneath this apparent paradox. Their findings are published in the open access journal BMC Biology.
裸鼹鼠群体由2只具有生殖能力的首领和大约300只没有生殖能力的工鼠组成。对于首领而言，繁殖会造成额外的能量消耗，鼠后在生育的基础上还要进行哺乳，本应因此削减寿命，但它们的寿命却比工鼠更长，且终生保有繁殖能力。德国莱布尼茨老年化研究所的研究者们调查了这一悖论背后的遗传学机制，他们的发现近期发表在了开放获取期刊《BMC生物学》（BMC Biology）上。

Dr Martin Bens, the corresponding author said: “Our results indicate that when naked mole-rats mature into breeders, it changes their aging rates, meaning that breeders are able to live longer than non-breeders. This is surprising, as evidence from other species suggest that reproduction, which ensures the survival of the species as a whole, reduces the lifespan of the individual. In naked mole-rats reproduction appears to prolong the breeders’ lifespan. This goes against the common expectation that mammals either invest resources in a long life or in reproduction.”
研究的通讯作者Martin Bens博士说：“我们的研究结果显示，当裸鼹鼠成熟发育出繁殖能力时，它们的衰老速率也同时被改变了，即首领能够比工鼠活得更久。这很让人吃惊，因为从其他物种身上找到的证据都表明，繁殖虽然对整个物种的生存有益，但却会削减个体的寿命。可是在裸鼹鼠中，生殖似乎可以延长寿命。这与哺乳动物要么将资源用来延长寿命、要么用来繁育后代的普遍认知相悖。”

The researchers analyzed the transcriptomes – the sum of all transcribed genes – for tissue samples taken from a range of organs, including heart, liver, and gonads. They compared the transcriptomes of naked mole-rat breeders to that of non-breeders, as well as to breeding and non-breeding guinea pigs, which are close relatives of the naked mole-rat but have a shorter lifespan.
研究者们从一系列器官（包括心脏、肝和性腺）中提取了组织样本，并对转录组——即所有被转录的基因——进行了分析。他们将有繁殖能力的裸鼹鼠的转录组与工鼠、有繁殖能力的豚鼠、无繁殖能力的豚鼠的转录组分别进行了比较，其中豚鼠是裸鼹鼠的近亲但寿命较短。

The authors found that genes related to aging were expressed differently in samples from breeding naked mole-rats than those from guinea pigs and non-breeding naked mole-rats. For example, a gene related to muscle regeneration showed higher expression in naked mole-rat breeders which may be linked to higher resistance to muscle loss during aging. Gene expression changes like this may contribute to the exceptionally long lifespan of naked mole-rat breeders.
作者发现有繁殖能力的裸鼹鼠，其衰老相关的基因的表达与另三者显著不同。比如，一个和肌肉再生相关的基因可能有利于抵抗衰老过程中的肌肉流失，这个基因在有繁殖能力的裸鼹鼠中的表达量更高。类似的基因表达变化可能为裸鼹鼠首领长得异乎寻常的寿命做出了贡献。

Dr Bens said: “Unlike non-breeding guinea pigs and other rodents, non-breeding naked mole-rats are not sexually dimorphic; they show no differences in body size, body mass or external genitalia, as well as few behavioral differences. One of the main and surprising findings of our study is that transcribed genes in non-breeding naked mole-rats also show no significant differences between females and males. However, we found that the transcriptome changes significantly when they mature into breeders.”
Bens博士说：“与不具备生殖能力的豚鼠或其他啮齿类动物不同，不具备生殖能力的裸鼹鼠不会有性别二态性，雌雄鼠之间体型、体重或外生殖器都没有差别，连行为上的差异都很小。我们的研究中最主要也最令人惊讶的发现之一，就是雌雄裸鼹鼠在转录的基因上也没有显著差异。但是我们发现当它们成熟为可繁殖个体后，转录组就会极大地改变。”

When the authors separated non-breeding naked mole-rats from colonies and paired them with naked mole-rats of the opposite sex, the workers transitioned into breeders. The transition was accompanied by physical and behavioral changes that differed between males and females – the animals became sexually dimorphic. Sexual maturation was also associated with a change in gene expression levels linked to extended life and health span.
当作者把没有生育能力的裸鼹鼠从群体中分离出来，并与异性裸鼹鼠配对后，工鼠便能恢复生育能力。这一转变过程伴随生理和行为上的变化，且雌雄两性的变化不同——也就是说这些动物此时会表现出性别二态性。性成熟的发生，也伴随着长寿和健康相关的基因在表达水平上的变化。

Dr Bens said: “Deeper investigations of naked mole-rat transcriptome data can help us understand how sexual maturation is regulated. This could potentially help us better understand sexual maturation in humans, where the onset of puberty varies between individuals and is influenced by a variety of factors such as stress and nutrition. Variations in puberty onset have implications for the risk for diseases such as breast cancer or cardiovascular diseases. Our data may help identify targets to mitigate these variations.”
Bens博士说：“对裸鼹鼠转录组数据的深入挖掘，可以帮助我们理解性成熟的调控机制。这可能可以让我们更好地理解人类的性成熟，不同的人青春期起始时间不同，又受很多因素（比如压力和营养）的影响。青春期的起始时间又与很多疾病（如乳腺癌或心血管疾病）的发生相关联。我们的数据可能有助于找到减轻这种差异的靶点。”

In another study titled ‘Species comparison of liver proteomes reveals links to naked mole-rat longevity and human aging,’ published in BMC Biology on the same day, Dr Bens and colleagues compared the liver of naked mole-rats with those of guinea pigs to further investigate the molecular mechanisms that underlie naked mole-rat longevity.
在同一天发表在《BMC生物学》上的另一个研究《肝脏蛋白质组的物种间比较揭示其与裸鼹鼠长寿及人类衰老的联系》（Species comparison of liver proteomes reveals links to naked mole-rat longevity and human aging）中，Bens博士与同事比较了裸鼹鼠和豚鼠的肝脏，以进一步研究裸鼹鼠长寿背后的分子机理。

Alessandro Ori, the corresponding author of the study said: “We found that naked mole-rat livers have a unique expression pattern of mitochondrial proteins that result in distinct metabolic features of their mitochondria, including an increased capacity to utilize fatty acids. We were also able to show that similar molecular networks are affected during aging in both naked mole-rats and humans, which suggests that there may be a direct link between these networks and the longevity of these species, both of which would be expected to have much shorter lives based on their body mass.”
这个研究的通讯作者Alessandro Ori说：“我们发现裸鼹鼠的肝脏在线粒体蛋白的表达上呈现出了一种特别的模式，导致它们的线粒体具备一些与众不同的代谢特征，其中包括较高的脂肪酸利用能力。我们还成功证明，无论是裸鼹鼠还是人类，在衰老过程中受影响的分子网络是类似的，这表明这些网络和这两个物种的长寿之间可能有直接的联系，必经按照体重估算他们的寿命本应短得多。”

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Notes to editor附注:

1. Research article原文1:

Bens et al. Naked mole-rat transcriptome signatures of socially-suppressed sexual maturation and links of reproduction to aging
BMC Biology 2018
DOI: 10.1186/s12915-018-0546-z

After the embargo lifts, the article will be available here:

2. 原文2：

Heinze et al. Species comparison of liver proteomes reveals links to naked mole-rat longevity and human aging
BMC Biology 2018
DOI: 10.1186/s12915-018-0547-y

During the embargo period, the article is available here: https://bit.ly/2uXD1w0

After the embargo lifts, the article will be available here:

限制令解除后，原文链接如下： https://bmcbiol.biomedcentral.com/articles//10.1186/s12915-018-0547-y

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