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Can we travel through space with the help of this tiny worm?
Biologists in Oslo have found out how hibernators can protect their cells from cold.
“You’re not dead till you’re warm and dead,” is a common saying in emergency medicine.
In 1999, 29 year old Anna Bågenholm survived a body temperature of 13,7°C, after a skiing accident sent her under ice in a river. Her heart did not beat for several hours.
Now, a group of researchers in Oslo have come closer to explaining what happens in cells that experience deep cooling.
A tiny ringworm may provide answers
Their work is relevant for both hibernation and accidental hypothermia. It has ramifications for treating trauma patients in hospitals, neurodegenerative diseases like Alzheimer’s and Parkinson’s.
In the future it might even help humans travel in space.
“This project began quite a few years ago as an ambitious masters’ project, where the student wanted to work on something cool. Obliging, we began studying proteins involved in cold responses,” says Rafal Ciosk, professor in the Section for Biochemistry and Molecular Biology at the Department of Biosciences, University of Oslo.
The researchers studied this in their favourite model organism, the nematode C. elegans (Caenorhabditis elegans). The tiny worm is just around 1 millimetre long and is widely used in biological research.
Hibernating worms prolong their lifespan
Through their research, Ciosk and his colleagues realised how little is known about organismal responses to cold.
They saw that if they cool the C. elegans in a particular way, they will survive for a very long time without affecting the total lifespan.
The researchers kept the worms at 4 degrees for a week, then took them out from the cold and measured their lifespan. Remarkably, the total life span was a week longer than that of animals cultivated in the normal temperature.
“It looked like they were hibernating, and this is something that has not been described for this organism before,” Ciosk says. “We started looking at what happens in this organism and, while doing genetics on this model, we realised that there are certain manipulations we can do that make the survival of these animals in the cold even more effective.”
An iron storing protein is the key
One particular gene manipulation that increases the levels of ferritin, a protein that stores iron, protected the worms from the cold.
Iron is an essential element for us, however free iron can be toxic. Ferritins make huge nano cages that can accommodate thousands of iron atoms, thus making it possible to store and transport iron in a safe and non-toxic way.
Ciosk explains they also tested whether this may be relevant for the mammalian cells. They chose neurons, nerve cells in the brain and nervous system, which are very sensitive cells.
“We found that when we induced ferritin in these cells, and exposed them to cold, the ferritin had protective effects,” he says.
The researchers also found that mimicking the effect of ferritin with drugs also had beneficial effects for the neurons.
Hibernating our way through space?
You might think the tiny C. elegans worm has very little in common with humans.
“The physiology is very different, but at the basic cellular level, many processes are conserved. The way the cell works is very similar across species,” Ciosk explains.
Hibernation is rare among primates, but there are examples of hibernating lemurs in Madagascar.
“In C. elegans and the neuron cells, we overexpressed ferritin and then showed that it has benefits. But, apparently, ferritin is expressed naturally in those hibernating primates. This could possibly be the way they survive the cold in nature,” Ciosk says.
Humans do not hibernate, but a hibernation-like sleep is suggested to facilitate long-distance space travel some time in the future.
Cooling trauma patients to 10 degrees
An application that is much nearer in time is cooling of patients in hospitals.
Ciosk explains that cooling is used in several ways clinically. With moderate cooling, the patient's body temperature is lowered to 32-33 degrees.
In deep cooling, however, the body temperature will be lowered to approximately 10 degrees. There are clinical trials exploring deep cooling at a hospital in the USA.
“This is in the range of hibernating animals,” Ciosk says.
Relevant for diseases like Alzheimer’s and Parkinson’s
The research conducted by the group in Oslo is also relevant for neurodegenerative diseases like Alzheimer’s and Parkinson’s.
“In the neurons we are experimenting on, we are looking at cold-related degeneration. A couple of years ago, a study showed that certain cold-induced proteins have protective effects against various neurodegenerative diseases,” Ciosk says. “So, if you find how hibernators protect their neurons in the cold you may also find pathways that are relevant for patients."
The next step for the researchers in Oslo is to take what they have found in C. elegans and cultured neurons and move it to an in vivo mammalian model.
Pekec et al. Ferritin-mediated iron detoxification promotes hypothermia survival in Caenorhabditis elegans and murine neurons, Nature Communicaions, vol. 13, 2022.
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