Immortal Jellyfish Study Offers Clues to Cell Repair

The tiny jellyfish Turritopsis dohrnii can reverse its life cycle. Scientists are studying the genetic processes behind that change for clues to rejuvenating human cells. The research asks whether cells and tissues might be coaxed into more youthful states to help heal wounds or treat age-related diseases—not to turn elderly people into babies, which one idea describes as science fiction.

How the jellyfish changes

Under stress, Turritopsis dohrnii stops moving and sinks to the bottom of its tank. It transforms into a ball of cells, unlike the tentacled, umbrella-shaped adult form known as the medusa. Within one to three days, a polyp buds from the ball and grows into a colony that eventually produces new medusae.

“From one jellyfish that doesn't die, then you get this colony that can form hundreds more,” said marine biologist Maria Miglietta of Texas A&M University at Galveston. Each new jellyfish can, in principle, rejuvenate in the same way.

Scientists first reported the species’ regenerative ability in 1992. An Italian scientist keeping the animals in a laboratory forgot to feed them over a weekend and returned expecting to find them dead. Instead, he found new polyps in the container, Miglietta said. Stefano Piraino, a biologist at Italy's University of Salento, later studied how the process might work.

Piraino found that certain tissues in the medusa undergo “transdifferentiation” during rejuvenation: they return to a stem-cell-like state and then specialise into other cell types. “Adult cells become ‘undifferentiated’ and become something else that is needed to form the polyp,” said Miglietta, who formerly worked in Piraino's lab.

What the genes may reveal

A 2022 study compared Turritopsis dohrnii genes with those of a related species not known to rejuvenate. Molecular biologist and bioinformatician Victor Quesada of the University of Oviedo in Spain cautioned that scientists can't be sure the related species lacks this ability, because many jellyfish remain understudied.

The comparison found that Turritopsis dohrnii had more copies of genes producing proteins that help repair mutations and other DNA damage that accumulates with age. It also had more copies of genes producing proteins involved in maintaining telomeres, caps at the ends of DNA strands that protect genetic material. Telomeres normally shorten with age, leaving DNA more vulnerable to damage.

Miglietta has compared genes activated at different life stages and studied genes active during the ball-like cyst stage, when cells reverse their fate and form new polyps. Research in 2019 and 2021 by Miglietta and colleagues found increased activity in genes with unknown functions, along with genes involved in DNA repair and telomere maintenance. A separate preliminary study by Miglietta found some overlap between genes overactivated during the cyst stage and genes linked to human longevity.

Possible uses—and limits

Michael Koldobskiy, a pediatric oncologist and physician-scientist at Johns Hopkins, said researchers would ultimately like to identify the molecular “switch” controlling the process and find out whether humans have the same switch. If they do, human cells might be encouraged into more youthful states to help heal wounds or tissue injured by strokes or heart attacks, or address damage associated with age-related vision loss or Alzheimer's disease.

“We're a long way away from harnessing that for human benefit,” Koldobskiy said. Scientists have found ways to induce rejuvenation-like processes in mammalian cells, but applying them to human tissues has proved difficult. He said studying the jellyfish may reveal more effective approaches.

The species lives across oceans from the Mediterranean to the Caribbean and Japan. But it is fragile: some animals in Miglietta's laboratory seem unable to rejuvenate, and those that can may eventually reach a limit and die of old age. Researchers don't know for sure, partly because the species is difficult to maintain in laboratories and appears to need specific conditions. In the wild, changing plankton availability, predators and algae that smother colonies may kill it.

Maria Pascual-Torner of Spain's Institute of Marine Sciences, who conducted the 2022 study with Quesada, called it “an extremely vulnerable organism” despite its ability to rejuvenate. “The immortal jellyfish also reminds us that life and death are inseparable parts of the same reality,” she said.