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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.

眾所周知灰熊有冬眠這一習性,然而它們的肌肉卻不會因為長達幾個月的缺乏運動而萎縮。在Michael Gotthardt領導的研究團隊的《科學報告》中,講述了它們如何做到這一點的?;倚艿牟呗砸部梢詭椭A防人類的肌肉萎縮。

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.


Understanding and copying the tricks of nature


“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.

“肌肉萎縮是在許多情況下都會發生真正的人類問題。而我們仍然不能很好的去應對它,”該研究的主要作者Douaa Mugahid博士說,Douaa Mugahi博士曾經是Gotthardt教授研究小組的成員,現在是波士頓哈佛醫學院系統生物學系的Marc Kirschner教授實驗室的博士后研究員。

“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說:“對我來說,我們的工作之美在于學習自然如何完善了在困難的冬眠條件下維持肌肉功能的方法?!?“如果我們能更好地理解這些策略,我們將能夠開發出新穎且可靠的方法來更好地預防和治療患者的肌肉萎縮?!?br />
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.

為了了解熊的策略,由Mugahid和Gotthardt領導的團隊在數個連續的冬天里檢查了灰熊的肌肉樣本,這是他們從華盛頓州立大學收到的。 Gotthardt解釋道:“通過將先進的測序技術與質譜分析法相結合,我們希望確定在冬眠期間以哪些基因和蛋白質被上調或關閉?!?br />
“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.


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.

為了找出哪些信號通路需要在肌肉中激活,Gotthardt和他的團隊比較了灰熊,人類和小鼠中基因的活性。所需數據來自老年患者或臥床不起的患者以及患有肌肉萎縮癥的小鼠,例如打了石膏之后活動減少的病患。 Gotthardt解釋說:“我們想找出相比于那些不冬眠的動物,冬眠動物的基因有哪些受到了調控?!?br />
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,科學家們遇到了一系列這樣的基因。為了縮小可能被證明是肌肉萎縮治療起點的候選對象范圍,研究小組隨后進行了線蟲蠕蟲實驗。 Gotthardt解釋說:“在蠕蟲中,單個基因可以相對輕松地失活,并且可以迅速看到其對肌肉生長的影響?!?br />
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.”

在這些實驗的幫助下,他的團隊現在已經發現了一些基因,他們希望通過這些基因的影響來進一步研究小鼠。其中包括參與葡萄糖和氨基酸代謝的基因Pdk4和Serpinf1,以及有助于晝夜節律發展的基因Rora。 Gotthardt說:“我們現在將研究使這些基因失活的作用?!?“畢竟,只有在副作用有限或根本沒有副作用的情況下,它們才適合作為靶向治療?!?/div>
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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.


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.


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.


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.


The amount of progress being made in the medicle field is stunning.


Clearly the correct answer is to start sending bears into space.


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


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


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


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

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.