The immortal jellyfish can beat ageing. It could inspire treatments for diseases of old age
Getty ImagesThe immortal jellyfish is capable of winding back its lifecycle to become young again. Scientists are unlocking its cellular secrets to find ways human cells could rejuvenate too.
The tiny translucent jellyfish Turritopsis dohrnii is surprisingly hard to kill. The marine biologist Maria Miglietta of Texas A&M University at Galveston has cut them, boiled them, starved them, overloaded their tanks with salt or plopped them in fresh water – but the nifty creatures seem to cheat death every time.
Under duress, they stop in their tracks and fall to the bottom of their tank. Then something astonishing happens: the animals transform into balls of cells that bear no resemblance to the tentacled umbrella shape of adult jellyfish, known as the medusa. Within one to three days, a structure called a polyp – an early jellyfish life stage – buds off from this ball of cells and then grows into a colony, which will eventually sprout new medusae.
"From one jellyfish that doesn't die, then you get this colony that can form hundreds more," Miglietta says. And each one of these new jellyfish can, in principle, rejuvenate the same way – exhibiting a seemingly endless capacity to wind back to the clock to youth.
Miglietta and other scientists are now studying the genetic and molecular processes that make Turritopsis dohrnii's death-defying feat possible. By unlocking these secrets, scientists eventually hope to explore whether they can trigger similar kinds of processes in humans. The goal is not to turn elderly people back into babies, Benjamin Button-style – an idea that's firmly in the realms of science fiction – but to coax cells and tissues into more youthful states to heal wounds and treat age-related maladies.
"The holy grail of this kind of thing, I think, would be regenerative biology: trying to reverse ageing-related degeneration or degradation," says Michael Koldobskiy, a pediatric oncologist and physician-scientist at Johns Hopkins. "We're a long way away from harnessing that for human benefit, but I think understanding these organisms that evolved these processes millions of years ago could potentially really pay off."
AlamyTurritopsis dohrnii's regenerative talents were first reported in 1992 by an Italian scientist who was keeping the animals in the lab and forgot to feed them over a weekend. Expecting to find them dead when he returned, "instead he found new polyps in the container", Miglietta says.
Soon, the biologist Stefano Piraino of Italy's University of Salento started to take an interest in what made this feat of rejuvenation possible. As embryos develop, so-called stem cells multiply and morph into the nerve cells, muscle cells and various other cell types that make up the body. Usually, they're stuck in that particular cell type until they age and die. But Piraino discovered that, during the immortal jellyfish's rejuvenation, certain tissues in the medusa undergo a "transdifferentiation" process where they revert back to a stem cell-type state and then specialise into other cell types.
"Adult cells become 'undifferentiated' and become something else that is needed to form the polyp," says Miglietta, who used to work in Piraino's lab.
Turritopsis dohrnii's ability to rejuvenate earned it the nickname "immortal jellyfish". It is – as far as scientists know – unique in the animal kingdom. While some lizards, worms and amphibians can regrow lost or injured body parts, none come close to reverting adult bodies back into babies. Turritopsis dohrnii is a remarkable demonstration that ageing and mortality is not always a biological inevitability (though scientists can't rule out that it doesn't eventually die naturally).
Genetic clues
Today, Miglietta and others are working to dissect the genetic processes that allow cells to go back in time. The ultimate dream, Koldobskiy says, would be to identify the molecular "switch" that controls this process. If the same control switch exists in humans, then perhaps it can be triggered to coax human cells to more youthful states. If possible, that could accelerate the healing of wounds or injured tissue after strokes or heart attacks, or perhaps even reverse the damage that occurs in age-driven vision loss or the neurodegeneration that happens in Alzheimer's disease.
"We're not going to shrink down to an embryo again and restart," he says, "but at the organ and tissue level, I think it's very much a possibility."
The research is young, but is already starting to reveal some clues. In a 2022 study, one team of researchers compared the genes of Turritopsis dohrnii and a related species that is not known to rejuvenate – though it's hard to be certain that it's not capable of doing so, as many jellyfish are understudied, says molecular biologist and bioinformatician Victor Quesada of the University of Oviedo in Spain.
Compared to the other species, Turritopsis dohrnii's DNA contained more copies of genes that produce proteins to help repair mutations and other kinds of DNA damage that accumulates with age. The immortal jellyfish also had more copies of genes that produce proteins involved in maintaining structures called telomeres – little caps on the end of DNA strands that protect the genetic material from damage. Normally, telomeres shorten with age, making the DNA more susceptible to damage, but the immortal jellyfish's enhanced ability to repair them could be one key to its longevity, Quesada says.
This is just the beginning of understanding the secrets of Turritopsis dohrnii's rejuvenation strategy and whether any aspect of it could be applied to humans, Quesada says.
"We assume in many diseases, that there's no way back," he says. "Perhaps there might be a way back, if we [learn] enough about… how those mechanisms work."
Davide Maggioni/Miglietta lab at Texas A&M GalvestonMiglietta, meanwhile, has been comparing the genes activated across Turritopsis dohrnii's different life stages and examining the ones that are only activated during the ball-like cyst stage, where cells reverse fate and then create new polyps. "That may be an indication that those genes are involved in that unique process," she says.
In 2019 and 2021 research, she and her colleagues found a heightened activity of mysterious genes with unknown functions, but also ones involved in repairing DNA and maintaining telomeres.
Another preliminary study by Miglietta found that there's some overlap in the genes being overactivated in the cyst stage and genes that have been linked to longevity in humans. That underscores the idea that there may be common pathways between the two species, Miglietta says.
Miglietta is now collaborating with Koldobskiy to better understand these processes and eventually explore whether they can be induced in human cells. Scientists have already discovered certain ways of inducing rejuvenation-like processes in mammalian cells, but applying this to human tissues has proven difficult. Perhaps studying Turritopsis dohrnii will reveal other, more effective ways of doing so, Koldobskiy hopes.
Fragility of an immortal organism
On top of its potential practical benefits in medicine, Turritopsis dohrnii also offers more philosophical lessons. "It's comforting to think that nature has found a solution to one of the main problems of humans: ageing and death," Miglietta says. And indeed, she suspects that Turritopsis dohrnii's incredible resilience is one reason why the species has become so widespread across the world's oceans, from the Mediterranean to the Caribbean and Japan.
But while it may seem invincible, the immortal jellyfish is also fragile. Miglietta says that there's a proportion of animals in her lab that seem incapable of rejuvenating. And among the ones that do, there may be an eventual limit to the number of times they can rejuvenate before dying of old age. It's hard to know for sure because it's difficult to maintain the species for long durations in the lab as it seems to require specific conditions to survive. And, in the wild, there's plenty of things that probably do kill them – including fluctuating availability of their plankton food, predators or algae that smother jellyfish colonies.
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As such, the immortal jellyfish offers an important lesson, says Maria Pascual-Torner of Spain's Institute of Marine Sciences, who conducted the 2022 study with Quesada. "Although it has the ability to rejuvenate and, theoretically, not die from ageing, it is at the same time an extremely vulnerable organism," she says. "The immortal jellyfish also reminds us that life and death are inseparable parts of the same reality." In other words, even nature's most immortal organism has to face death.
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