熊可以冬眠 人为什么不行 特殊氨基酸是关键
2022-06-11 s555555555 4794
正文翻译

Grizzly bears spend many months in hibernation, but their muscles do not suffer from the lack of movement. In the journal “Scientific Reports”, a team led by Michael Gotthardt reports on how they manage to do this. The grizzly bears’ strategy could help prevent muscle atrophy in humans as well.

众所周知灰熊有冬眠这一习性,然而它们的肌肉却不会因为长达几个月的缺乏运动而萎缩。在Michael Gotthardt领导的研究团队的《科学报告》中,讲述了它们如何做到这一点的。灰熊的策略也可以帮助预防人类的肌肉萎缩。

A grizzly bear only knows three seasons during the year. Its time of activity starts between March and May. Around September the bear begins to eat large quantities of food. And sometime between November and January, it falls into hibernation. From a physiological point of view, this is the strangest time of all. The bear’s metabolism and heart rate drop rapidly. It excretes neither urine nor feces. The amount of nitrogen in the blood increases drastically and the bear becomes resistant to the hormone insulin.

一只灰熊只知道一年有三个季节。它的活动时间从三月到五月开始。九月左右,熊开始吃大量的食物蓄积能量。在十一月到一月之间的某个时候,它陷入了休眠状态。从生理的角度看,这是最奇怪的时刻。熊的新陈代谢和心率迅速下降。它既不排尿也不排泄粪便。血液中的氮含量急剧增加,而此时熊对胰岛素也不产生反应。

A person could hardly survive this four-month phase in a healthy state. Afterwards, he or she would most likely have to cope with thromboses or psychological changes. Above all, the muscles would suffer from this prolonged period of disuse. Anyone who has ever had an arm or leg in a cast for a few weeks or has had to lie in bed for a long time due to an illness has probably experienced this.

一个正常人一觉睡了四个月还想正常起来那是不可能的。之后,他或她将最有可能应对血栓形成或心理变化方面的问题。最重要的问题是,肌肉遭受长时间的停用就会萎缩。曾经手臂或腿打了石膏几个星期动不了或因病不得不长时间卧床的人可能经历过这种情况。

Not so the grizzly bear. In the spring, the bear wakes up from hibernation, perhaps still a bit sluggish at first, but otherwise well. Many scientists have long been interested in the bear’s strategies for adapting to its three seasons.

但灰熊就不一样了。在春天,熊从冬眠中醒来,一开始也许还有些呆滞,但其他方面都没有问题。长期以来,许多科学家一直对熊的适应三个季节的策略感兴趣。

A team led by Professor Michael Gotthardt, head of the Neuromuscular and Cardiovascular Cell Biology group at the Max Delbrück Center for Molecular Medicine (MDC) in Berlin, has now investigated how the bear’s muscles manage to survive hibernation virtually unharmed. The scientists from Berlin, Greifswald and the United States were particularly interested in the question of which genes in the bear’s muscle cells are transcribed and converted into proteins, and what effect this has on the cells.

柏林马克斯·德布吕克分子医学中心(MDC)肌肉神经和心血管细胞生物学小组组长Michael Gotthardt教授领导的研究小组现在研究了熊的肌肉细胞如何在几乎不受伤害的冬眠中生存下来。来自柏林,格赖夫斯瓦尔德和美国的科学家对熊的肌肉细胞中的哪些基因被转录并转化为蛋白质以及对细胞有什么影响的问题特别感兴趣。
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Understanding and copying the tricks of nature

了解和复制自然的窍门
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“Muscle atrophy is a real human problem that occurs in many circumstances. We are still not very good at preventing it,” says the lead author of the study, Dr. Douaa Mugahid, once a member of Gotthardt’s research group and now a postdoctoral researcher in the laboratory of Professor Marc Kirschner of the Department of Systems Biology at Harvard Medical School in Boston.

“肌肉萎缩是在许多情况下都会发生真正的人类问题。而我们仍然不能很好的去应对它,”该研究的主要作者Douaa Mugahid博士说,Douaa Mugahi博士曾经是Gotthardt教授研究小组的成员,现在是波士顿哈佛医学院系统生物学系的Marc Kirschner教授实验室的博士后研究员。

“For me, the beauty of our work was to learn how nature has perfected a way to maintain muscle functions under the difficult conditions of hibernation,” says Mugahid. “If we can better understand these strategies, we will be able to develop novel and non-intuitive methods to better prevent and treat muscle atrophy in patients.”

Mugahid说:“对我来说,我们的工作之美在于学习自然如何完善了在困难的冬眠条件下维持肌肉功能的方法。” “如果我们能更好地理解这些策略,我们将能够开发出新颖且可靠的方法来更好地预防和治疗患者的肌肉萎缩。”

To understand the bears’ tricks, the team led by Mugahid and Gotthardt examined muscle samples from grizzly bears both during and between the times of hibernation, which they had received from Washington State University. “By combining cutting-edge sequencing techniques with mass spectrometry, we wanted to determine which genes and proteins are upregulated or shut down both during and between the times of hibernation,” explains Gotthardt.

为了了解熊的策略,由Mugahid和Gotthardt领导的团队在数个连续的冬天里检查了灰熊的肌肉样本,这是他们从华盛顿州立大学收到的。 Gotthardt解释道:“通过将先进的测序技术与质谱分析法相结合,我们希望确定在冬眠期间以哪些基因和蛋白质被上调或关闭。”

“This task proved to be tricky – because neither the full genome nor the proteome, i.e., the totality of all proteins of the grizzly bear, were known,” says the MDC scientist. In a further step, he and his team compared the findings with observations of humans, mice and nematode worms.

MDC的科学家说:“这项任务非常棘手-因为我们既不了解完整的基因组,也不了解蛋白质组,即不知道灰熊所有的蛋白质。”下一步,他和他的团队将这些发现与人类,小鼠和线虫蠕虫的观察结果进行了比较。

As the researchers reported in the journal “Scientific Reports”, they found proteins in their experiments that strongly influence a bear’s amino acid metabolism during hibernation. As a result, its muscle cells contain higher amounts of certain non-essential amino acids (NEAAs).

正如研究人员在《科学报告》杂志上所报道的那样,他们在实验中发现了蛋白质,这些蛋白质在休眠期间会严重影响熊的氨基酸代谢。结果就是,其肌肉细胞含有更多的某些非必需氨基酸(NEAA)。

“In experiments with isolated muscle cells of humans and mice that exhibit muscle atrophy, cell growth could also be stimulated by NEAAs,” says Gotthardt, adding that “it is known, however, from earlier clinical studies that the administration of amino acids in the form of pills or powders is not enough to prevent muscle atrophy in elderly or bedridden people.”

Gotthardt教授说:“我们在人类和小鼠的分离出的肌肉细胞表现出肌肉萎缩的实验中发现,NEAA也可以刺激这些细胞生长。”,“但是,从早期的临床研究中可以知道,氨基酸以药片或散剂的形式是并不足以防止老年人或卧床不起的人出现肌肉萎缩的。”

“Obviously, it is important for the muscle to produce these amino acids itself – otherwise the amino acids might not reach the places where they are needed,” speculates the MDC scientist. A therapeutic starting point, he says, could be the attempt to induce the human muscle to produce NEAAs itself by activating corresponding metabolic pathways with suitable agents during longer rest periods.

MDC科学家推测:“显然,肌肉自身产生这些氨基酸很重要-否则氨基酸可能无法到达需要它们的地方。”他说,治疗的起点可能是尝试通过在较长的卧床不起时间段内用合适的药物激活相应的代谢途径来诱导人的肌肉自身产生NEAA。

Tissue samples from bedridden patients
In order to find out which signaling pathways need to be activated in the muscle, Gotthardt and his team compared the activity of genes in grizzly bears, humans and mice. The required data came from elderly or bedridden patients and from mice suffering from muscle atrophy – for example, as a result of reduced movement after the application of a plaster cast. “We wanted to find out which genes are regulated differently between animals that hibernate and those that do not,” explains Gotthardt.

为了找出哪些信号通路需要在肌肉中激活,Gotthardt和他的团队比较了灰熊,人类和小鼠中基因的活性。所需数据来自老年患者或卧床不起的患者以及患有肌肉萎缩症的小鼠,例如打了石膏之后活动减少的病患。 Gotthardt解释说:“我们想找出相比于那些不冬眠的动物,冬眠动物的基因有哪些受到了调控。”

However, the scientists came across a whole series of such genes. To narrow down the possible candidates that could prove to be a starting point for muscle atrophy therapy, the team subsequently carried out experiments with nematode worms. “In worms, individual genes can be deactivated relatively easily and one can quickly see what effects this has on muscle growth,” explains Gotthardt.

但是,科学家们遇到了一系列这样的基因。为了缩小可能被证明是肌肉萎缩治疗起点的候选对象范围,研究小组随后进行了线虫蠕虫实验。 Gotthardt解释说:“在蠕虫中,单个基因可以相对轻松地失活,并且可以迅速看到其对肌肉生长的影响。”
原创翻译:龙腾网 http://www.ltaaa.cn 转载请注明出处


A gene for circadian rhythms
With the help of these experiments, his team has now found a handful of genes whose influence they hope to further investigate in future experiments with mice. These include the genes Pdk4 and Serpinf1, which are involved in glucose and amino acid metabolism, and the gene Rora, which contributes to the development of circadian rhythms. “We will now examine the effects of deactivating these genes,” says Gotthardt. “After all, they are only suitable as therapeutic targets if there are either limited side effects or none at all.”

在这些实验的帮助下,他的团队现在已经发现了一些基因,他们希望通过这些基因的影响来进一步研究小鼠。其中包括参与葡萄糖和氨基酸代谢的基因Pdk4和Serpinf1,以及有助于昼夜节律发展的基因Rora。 Gotthardt说:“我们现在将研究使这些基因失活的作用。” “毕竟,只有在副作用有限或根本没有副作用的情况下,它们才适合作为靶向治疗。”

评论翻译
[–]At_Work_SND_Coffee
I wonder if this might be able to give us a way to defeat muscle atrophy for coma patients and anyone working in space for long duration''s of time.

我想知道这是否能为我们提供一种治疗肌肉萎缩的方法来治愈那些长期昏迷的病人和任何长期在太空工作的人。

[–]BocceBaller42[S]
The article mentions that attempts to take supplements hasn''t helped bedridden patients and that a key difference is the bears make/deliver the amino acids themselves to the spots that need it.

这篇文章有提到,尝试服用补充剂对卧床不起的病人没有帮助,关键的区别是熊自己制造/运送氨基酸到需要它的地方。

[–]At_Work_SND_Coffee
Sounds like something we''ll need to build our medical monitoring equipment around, if we can identify these things it will result in easier recovery for coma/paralysis victims and space travelers.

听起来我们需要建立我们的医疗监控设备,如果我们能识别出这些氨基酸到底是什么东西,将会使昏迷/瘫痪的病人和太空旅行者更容易恢复。

[–]Havanatha_banana
Even if we could, are we able to deliver it to localised areas? I thought that one of the difficulty of medicinal administration is delivery to certain areas.

即使我们可以,我们能把它送到细胞内部吗?我认为给药的困难之一就是是把药精准地送到某些位置。

[–]Azureraider
It is a difficult problem, but it''s also a problem a lot of people are working on. Targeted delivery of drugs is a big deal for new cancer therapies.

这是个困难的问题,但也是很多人正在努力解决的问题。靶向给药对于新型癌症治疗来说是首要问题。
原创翻译:龙腾网 http://www.ltaaa.cn 转载请注明出处


[–]hamsterkris
I wonder if nanotechnology will solve that. If a tiny robot with a capsule of medicin can localize itself in the body and release it when needed that could do the trick.

我想知道纳米技术能否解决这个问题。如果一个微型机器人能在体内定位并在需要时释放药物,就能达到这个目的。

[–]Ambstudios
I think we’d be more likely to see some form of tech that can essentially work you out while immobile. If nanotech does become possible I feel it would almost be better for them to go make small tears in the muscles forcing the body to repair itself in the same way working out affects the body.

我认为我们更有可能看到某种形式的技术,可以在你不动的情况下解决你的问题。如果纳米技术真的成为可能,我觉得对他们来说,在肌肉上做点小小的撕裂,迫使身体自我修复,就像运动影响身体一样,会更好。

[–]milkplantation
They tried this for awhile with CPM (continuous passive movement) machines to prevent the massive muscle atrophy that occurs during recovery from an ACL surgery. It did little to alleviate swelling or reduce atrophy.
Maybe nano can offer a better alternative.

他们用CPM(持续被动运动)器械尝试了一段时间,以防止韧带手术恢复过程中出现的大量肌肉萎缩。然而这几乎没有缓解肿胀或减少萎缩。
也许纳米技术可以提供更好的选择。

[–]Throwitupyourbutt
The amount of progress being made in the medicle field is stunning.

医疗行业日新月异的发展进步真是让人惊叹。

[–]Olibri
Clearly the correct answer is to start sending bears into space.

很明显把灰熊送上太空就能得到正确答案了。

[–]Fez_and_no_Pants
If we can figure out a way to do it for all the cells... Hypersleep and or immortality, maybe?

如果我们能搞清楚所有细胞的机制的话。。长时间休眠甚至是永生都是可行的了?

[–]DrCaesars_Palace_MD
Immortality is a stretch. It''ll prevent muscle atrophy, but cells replication process is flawed and gets worse over time. It''s theorized that this is a major contributor to why we age,I believe. Our bodies can''t keep up

永生是一种延伸。它可以防止肌肉萎缩,但细胞复制过程是有缺陷的,而且随着时间的推移会变得更糟。我相信,从理论上讲,这是我们变老的主要原因。我们的身体跟不上

[–]fAP6rSHdkd
Manufactured replacement parts would work for organs. Bones would be harder and skin would be very difficult to fully replace, but making tailormade parts with your own DNA code and enough telomeres to add 100 years to their life expectancy sounds possible in the next 30-50 years. Replacing brains however that''ll take much longer unless we''re supplementing with computer hardware

人造的替换零件可以替换器官。但骨头会变得更硬,皮肤也很难完全替换,但用你自己的DNA代码和足够的端粒来制造定制的部件,让它们的预期寿命增加100岁,在未来30-50年听起来是可能的。然而,除非我们用电子硬件,否则要替换人脑将需要更长的时间
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[–]fAP6rSHdkd
Yep, it''s likely unsustainable for a population of 7 billion or at least it will be at first, but our kids or grandkids might not have to die from the normal aging process ever again and that''s a cool concept to me. What kinda laws and regulations will pop up around it? Will people rush to save up tens of millions of dollars to have these surgeries and retire for half their lifetime with a young body? What sort of philanthropic or passion projects will be possible for people who don''t need to work for a living because it''s viable to save up for a body replacement? Or will they save up to have the surgery and go back to work to save up for the next one? Will we stop at traditional organs or move on to mechanical parts? The great thing is that if we don''t implode as a species, the options are neigh endless and it all starts this century. Sorry if this seems too SciFi for thus point in time, but we will live to see all of these things come to fruition and that''s exciting to me

是的,对于70亿的人口来说,这可能是不可持续的,至少一开始是这样的,但是我们的孩子或孙子可能不会再死于正常的衰老过程,这对我来说是一个很酷的概念。会有什么样的法律法规围绕它出现呢?人们会急着攒下几千万美元去做这些手术,然后在退休后享受半辈子年轻的身体吗?对于那些不需要为了生活而工作的人来说,因为可以存下钱来进行身体替换手术,那么什么样的慈善或激情项目是可行的呢?或者他们会存钱去做手术,然后回去工作,为下一次手术存钱?我们会停留在传统的器官上,还是会转向机械部件?伟大的事情是,如果我们不作为一个普通物种自爆,选择是无尽的,这一切都开始于本世纪。对不起,如果这看起来太科幻了,在这个时间点,但我们会活着看到所有这些事情都实现,想想就让我异常兴奋
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[–]PastaBob
Depending on your current age, yes some people alive today could see a form of this at some point.

能不能看到要看你现在多少岁吧,是的很多年轻人有机会看到新时代的到来。
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[–]chrisjdel
There are already drugs ready to go to clinical trial which can reverse the aging process - to a degree. The ones they''re getting ready to test don''t actually rebuild telomeres, but they could add decades to a person''s life. A lot of people under age 65 right now could theoretically stay ahead of the curve as new developments occur.
As for what you do when humans have functional immortality (i.e. aren''t indestructible but don''t get sick or grow old) that''s pretty simple: childbirth must be regulated. Only when slow attrition whittles down the population to a certain point, or we''re ready to embark on a colonization effort, do you allow people to reproduce at will for a while. Probably best to have the kids all at once over a twenty or thirty year span and then stop, instead of a steady trickle being born all the time. That way children always have a sizable peer group to grow up with.
Personally, I think the world would benefit tremendously from everyone having a personal stake in the long-term future. Shortsighted thinking and decision making is killing us!

已经有药物准备进入临床试验,可以在一定程度上逆转衰老过程。他们准备测试的染色体端粒实际上并不能重建端粒,但却可以延长一个人几十年的寿命。从理论上讲,随着新形势的发展,许多65岁以下的人现在可以得到寿命延长。
至于当人类拥有功能性永生(即不是坚不可摧,但不会生病或变老)时,你会怎么做,那很简单:生育必须受到监管。只有当缓慢的消耗将种群数量减少到一定程度,或者我们准备开始殖民其它地方时,你才会允许人们随意繁殖一段时间。也许最好是在二、三十年的时间里一次性生完孩子,然后就停止,而不是一直稳定地慢慢生下来。这样,孩子们在成长过程中就会有一个相当大的同伴群体。
就我个人而言,我认为每个人都能从长远的未来中获益。短视的思维和决策无异于谋财害命!

[–]EssenceOfSenescence
Telomeres are not the whole story. All forms of cancer in humans involve telomere expansion because it allows cells to evade senescence, an anti-tumour mechanism. There are other ways we age as well, like accumulation of mutations, ROS, mitochondrial dysfunction, etc. also adding 100 years to our life expectancy within the next 30-50 years sounds quite optimistic. We can’t even make worms live twice as long and they have about 1000 cells and don’t really have organs the way we do... once we figure this stuff out in worms, flies, and mice, MAYBE we can begin to create therapies in humans. But we can’t even solve aging in simple organisms at the moment, and we don’t even know what even causes ageing either, so there’s a lot to consider when coming up with a timeline.

端粒并不是全部。人类所有形式的癌症都涉及到端粒的扩展,因为它使细胞逃避衰老,这是一种抗肿瘤机制。我们也有其他衰老的方式,比如突变、活性氧、线粒体功能障碍等的积累,也让我们在未来30-50年的预期寿命增加100年听起来相当乐观。然而我们现在甚至不能让小小的蠕虫多活一倍的寿命,它们有大约1000个细胞,而且没有我们这样的器官……一旦我们在蠕虫、苍蝇和老鼠身上发现了这些东西,也许我们可以开始在人类身上创造治疗方法。但我们现在甚至不能解决简单生物的衰老问题,我们甚至不知道是什么导致衰老,所以在人类发展的时间线上我们还要考虑许多问题。

 
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