Immortal Jellyfish Offers Clues to Cell Rejuvenation

Turritopsis dohrnii can reverse its life cycle under stress, changing from an adult jellyfish into a ball of cells that can produce a new colony. Scientists are studying the genes behind this transformation for clues to human tissue repair, but practical applications for people remain far off.

When stressed, the tiny, translucent jellyfish stops moving and sinks to the bottom of its tank. Within one to three days, a polyp buds from the ball of cells and grows into a colony, which eventually produces new adult jellyfish, called medusae. “From one jellyfish that doesn't die, then you get this colony that can form hundreds more,” said Maria Miglietta, a marine biologist at Texas A&M University at Galveston.

How the Jellyfish Reverses Its Life Cycle

Miglietta has cut, boiled and starved the animals, overloaded their tanks with salt, and put them in fresh water. They have repeatedly seemed to evade death. Some jellyfish in her lab, though, appear unable to rejuvenate, and researchers don't know whether those that can do so eventually hit a limit and die of old age.

Scientists first reported the ability in 1992. An Italian scientist who kept the jellyfish in a laboratory forgot to feed them over a weekend. He expected to find them dead, but instead found new polyps in the container, Miglietta said. Stefano Piraino, a biologist at Italy's University of Salento, later investigated how the process might work.

Piraino found that some medusa tissues undergo “transdifferentiation” during rejuvenation. Cells return to a stem-cell-like state, then develop into other cell types. “Adult cells become 'undifferentiated' and become something else that is needed to form the polyp,” Miglietta said.

What the Genetic Studies Found

A 2022 study compared the jellyfish's genes with those of a related species not known to rejuvenate. Victor Quesada, a molecular biologist and bioinformatician at the University of Oviedo in Spain, cautioned that researchers have studied many jellyfish only sparingly, so they can't be sure the related species truly lacks the ability.

Compared with that species, Turritopsis dohrnii had more copies of genes that produce proteins involved in repairing mutations and other DNA damage. It also carried more copies of genes associated with maintaining telomeres, protective caps at the ends of DNA strands that normally shorten with age. Quesada said its greater ability to maintain telomeres could be one factor in the jellyfish's longevity.

Research by Miglietta and colleagues in 2019 and 2021 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.

Human Applications Remain Uncertain

Michael Koldobskiy, a pediatric oncologist and physician-scientist at Johns Hopkins, said researchers hope to identify the molecular “switch” that controls the jellyfish's transformation and find out whether humans have the same switch. If they do, researchers might encourage human cells to enter more youthful states, helping repair wounds or tissue injured by strokes or heart attacks, or address damage associated with age-related vision loss or Alzheimer's disease.

“It's a long way away from harnessing that for human benefit,” Koldobskiy said. He said the aim isn't to turn elderly people into babies. “We're not going to shrink down to an embryo again and restart,” he said, “but at the organ and tissue level, I think it's very much a possibility.” Scientists have triggered rejuvenation-like processes in mammalian cells, but applying them to human tissues has proved difficult.

The species lives in oceans from the Mediterranean to the Caribbean and Japan. Its wide distribution may reflect its resilience, Miglietta said, but the jellyfish also faces threats: changing plankton availability, predators and algae that smother colonies may kill it in the wild. Maria Pascual-Torner of Spain's Institute of Marine Sciences called it “an extremely vulnerable organism.”