Unlocking the secrets of jumbo squid hibernation might improve human medicine
Jumbo squid switch off almost half of their overall metabolism when they hibernate on a daily basis
Originally published on September 19, 2020.
Jumbo squid are ferocious predators that emerge from the ocean depths at night to hunt. But while they are in the depths, they are in a deep state of hibernation, in which fully half their metabolism is shut down. Now scientists think they've figured out the genetic tricks that allow jumbo squid to go into this state of suspended animation.
"One of the reasons the squid do this, along with any other animal that hibernates, is mainly to conserve energy. Because when these squid are going down 200, 300 meters into the ocean's oxygen minimum zone, they don't have a lot of oxygen, which means they can't really metabolize things the way they would at the surface," said researcher Hanane Hadj-Moussa. Hadj-Moussa is a Ph.D candidate at Carleton University.
By figuring out how hibernating animals do this, scientists hope to apply those genetic tricks in human medicine, for example to safely induce medical hypothermia to reduce blood flow in injured patients, to improve organ transplants and even to reduce blood clots.
The way hibernating animals like squid get into their metabolically depressed state is by epigenetically modifying protein production, and thus reducing activity in the cell.
When male ground squirrels wake up in the spring, they have to grow a pair because they've regressed their gonads down to almost nothing.- Kenneth Storey, Carleton University
This is a fast way for cells to turn specific genes on or off in response to the environment. Hadj-Moussa found that the squid do this by using tiny strands of genetic material called microRNA that can act like a dimmer switch on specific genes, blocking proteins from getting made.
"That way they're able to turn off very specific processes that they don't need whilst keeping processes that they do need," she told Quirks & Quarks host, Bob McDonald.
"About 52 per cent of global metabolism was shut down, which is a significant amount."
Shutting down non-essential processes
One system that's largely shut down is their muscles, which are not used during their deep-water inactivity. At the same time, systems are activated to protect neurons in the brain.
Hadj-Moussa said they're finding very similar strategies in all the hibernating animals they study, including lemurs, frogs, bears and squirrels.
"We have found very universal themes, like energy conservation. You want to make sure that you can maintain energy and run everything at a low switch."
Another way hibernating animals do that is by selectively kickstarting a tissue-specific process called autophagy where the cell literally starts eating itself, so the tissues they don't need go away.
When ground squirrels emerge in the spring after hibernating all winter, their guts shrink to about half their original weight, but their hearts remain unaffected because they need to keep beating.
Guts aren't the only thing that shrink. "When male ground squirrels wake up in the spring, they have to grow a pair because they've regressed their gonads down to almost nothing," said Kenneth Storey, a professor of biochemistry at Carleton University and the senior scientist in these studies.
Co-opting hibernation tricks for biomedical applications
Invertebrates like jumbo squid give scientists like Hadj-Moussa and Storey insight into the basic processes that allow hibernating animals to survive in a metabolically depressed state. In some ways its a simpler system to study. Mammals are more complex in the processes they use to hibernate.
A good example are lemurs, non-human primates from Madagascar, that only drop their temperature by a few degrees when they're hibernating, which is about the same temperature that can induce medical hypothermia in humans.
You can inject and treat humans with little pieces of RNA that can regulate things. And there's a lot of trials going on right now, but it is in the early phases.- Hanane Hadj-Moussa, Carleton University
Hadj-Moussa and Storey also found that when lemurs hibernate, they turn down their metabolism by up to 90 per cent.
They hope that by learning how lemurs, and other hibernating animals turn down their metabolism, they can figure out how to use similar strategies to improve how to put patients into a medically induced hypothermic state, which can be useful for treatment of severe injuries.
"You can inject and treat humans with little pieces of RNA that can regulate things. And there's a lot of trials going on right now, but it is in the early phases," said Hadj-Moussa.
Other potential applications scientists are exploring include organ donation. Hibernation strategies might, for example, be used to keep harvested organs healthy without having to put them on ice, which can damage the tissues. They might also reveal a way to reduce blood clots, which hibernating animals that don't move around that much seem to avoid.
Produced and written by Sonya Buyting