The Incredible Way This Jellyfish Goes Back in Time

At the second conference of the Hydrazone Society, a paper was presented that was so revolutionary that members of the audience found it hard to believe. One attendee, a respected marine biologist, stated that the observation from the paper was, in fact, totally impossible and made completely by mistake.

In the late 1980s, two laboratory students collected a hydrazone specimen that they believed to be *Turitopsis nutricula*, a tiny jellyfish less than a centimeter long. The individuals they collected were in their immature adult medusae form, meaning they were not sexually mature yet and unable to release eggs and sperm. They placed the specimens in a tank, hoping to breed them for research purposes, and forgot about them. When they returned, they expected to find sexually mature adults; instead, they found fewer adult medusas than when they started and many babies in the form of newly settled polyps on the bottom of the tank.

Had these jellyfish reproduced that quickly? If they did, what happened to all of the adults? To find out, the researchers started to keep a close watch on the individuals in the tank, and what they found shocked them. The adult medusas were not spawning and reproducing to create new baby polyps; they were reverting back into their juvenile form, completely reversing the aging process. What they had collected was not *Turitopsis nutricula*, but a different jellyfish, *Turritopsis dohrnii*, which is capable of rejuvenating itself repeatedly, leading scientists to learn they had discovered something inconceivable: immortality.

In a world obsessed with aging and mortality, the media went crazy over this news. What is this tiny jellyfish’s secret to eternal youth? Can it really live forever? And if it can, how might we be able to harness this age-reversing secret for ourselves?

To understand how *Turritopsis dohrnii* achieves this amazing feat, it’s useful to look at its normal life cycle. The immortal jellyfish is not a true jellyfish but a hydrozoan that spends most of its life in its hydroid stage. The life cycle of this jellyfish starts when adult jellyfish in their recognizable medusae form swarm and release millions of eggs and sperm. Most species of jellyfish will swarm in the hundreds or even thousands for the purpose of reproducing. When a sperm successfully fertilizes an egg, the fertilized egg will grow into a planula, a tiny floating larva. Within a day or two, the planula will stick to a hard surface like the seafloor, a rock, or a coral. Once stuck, it starts growing up from its perch, forming a polyp that looks a bit like a plant with a long stem and a bulbous head, which now has a mouth and long waving tentacles. The polyp eats by sucking in food through its mouth, using its tentacles to help grab it.

Now, the polyps turn into a production line, creating a stack of cloned jellyfish. When the most mature clone is ready, it’s released and floats off into the water as a tiny version of a jellyfish called a ephyra. Alone in the ocean, all it has to do is eat and grow, eventually turning into the medusa we all recognize. For most jellyfish, this is the end of the line; they stay as medusas, swimming, eating, and spawning until they die. However, *Turritopsis dohrnii* has a unique ability to circumvent death. When this tiny jellyfish experiences high levels of stress, starvation, or physical damage, it can send all of its cells back into a younger state. The jellyfish shrinks and retracts its tentacles, and the medusa turns into a blob-like structure called a cyst that settles onto the ocean floor, just like its earlier self. Within three days, the blobby cyst starts growing into a polyp, and the whole process starts over.

This remarkable process has never actually been observed in the wild, only in the lab, but there’s no reason to think it isn’t occurring throughout our oceans. So, how does an adult jellyfish turn back into a baby? The immortal jellyfish can achieve this rejuvenation through a process called cellular transdifferentiation, where a cell of one type turns into an entirely different type of cell directly, without turning into a neutral intermediate form first. Studies have shown that the medusa doesn’t seem to contain stem cells, which are cells that have the potential to become any kind of cell, so it must be the case that its existing cells are repurposed.

Scientists have found that the cells of the top layer of the dome shape of the medusa and the canal system, which is essentially the jellyfish’s digestive system, are the most likely to be transformed into new cell types. The cells that make up the dome of a medusa are different from the cells that make up a polyp, as they have different roles suited to different needs. Through transdifferentiation, the immortal jellyfish can get these specialized medusa cells to turn into polyp cells. This reversal of development challenges common ideas about aging across the animal kingdom. It’s long been believed that sexual maturation marks a point of no return, where cells are stuck doing what they will always do until they reach senescence, or cell death. However, the immortal jellyfish can turn cells back into their earlier state at any point in their life cycle, whether they are a newly produced medusa or an older individual on the verge of death. All that’s needed is a bit of shock; in the first experiments proving this phenomenon, a pinch with some tweezers was enough to induce reversion.

We still don’t know exactly how *Turritopsis dohrnii* does it, but scientists have examined the cells of the cyst form of the immortal jellyfish and found some interesting differences compared to its polyp state that could provide insights into how the immortal jellyfish prepares for its new life. While in its cyst form, *Turritopsis dohrnii* spends a significant amount of its energy on internal upkeep, particularly looking after its DNA. The jellyfish seems to be able to protect and repair its telomeres. Telomeres are strands of DNA found at the end of chromosomes, and they protect the rest of our DNA from damage, especially during cell replication. Each time a cell replicates, a little bit of DNA is lost from the telomeres, but because they are extremely long, there is a lot to lose before any important DNA is affected. Eventually, telomeres can be ground down to nothing, making DNA more prone to damage, leading to cell death and ultimately the death of an organism. This process, known as telomere shortening, is a key element of aging in humans.

However, in *Turritopsis dohrnii* cysts, there seems to be a particularly high number of genes expressed that promote telomerase, an enzyme that repairs telomeres. With large amounts of this enzyme, the immortal jellyfish could be protecting its cells from natural aging by simply elongating the telomeres and safeguarding its DNA. Additionally, when in its cyst stage, the jellyfish spends little effort on replication or cell differentiation, which makes sense as it is actively trying to prevent cells from specializing. The cysts also do not respond to external stimuli, ensuring that they focus all their energy on DNA repair and maintenance until they are ready to become a polyp once more.

This strategy has worked well for *Turritopsis dohrnii*, which is rapidly taking over the world’s oceans. Originally from the Mediterranean, it is believed that they have hitchhiked on boats and are now found almost everywhere. Their resilience has likely contributed to their ability to survive across long distances and various environments. Researchers have found that in the lab, a single *Turritopsis dohrnii* is able to regenerate ten times at intervals as short as one month. In the wild, this could continue for much longer, possibly forever, in an eternal loop of back-and-forth transdifferentiations.

While it’s unlikely that we’ll ever be able to rejuvenate ourselves like *Turritopsis dohrnii*, there are lessons we can learn from this jellyfish that could help us combat some of the diseases that plague us later in life. Transdifferentiation is an intriguing field for scientists; being able to turn one cell into another in few to no steps and over a short period could open doors to treatments for conditions like Parkinson’s disease. Imagine if we could turn skin cells into neuronal cells to replace lost or damaged cells in the brain. Understanding how the immortal jellyfish accomplishes this could help us figure out how to do it ourselves.

Another area where the immortal jellyfish could provide insights is in microRNAs. These are short strands of genetic material that regulate our DNA, switching genes on and off and playing a role in DNA repair. We know that a lot of DNA repair occurs in regenerating *Turritopsis dohrnii*, and learning more about how microRNAs act to regulate DNA repair in these jellyfish could help us do the same for our own cells.

That said, while humans and jellyfish share some similarities in their DNA, we diverged on the tree of life some time ago, and there are genes in jellyfish that aren’t expressed in humans and vice versa. Therefore, there may be limitations to what is applicable. Even though *Turritopsis dohrnii* was first discovered in 1883, we only learned it might be immortal in the 1980s, and we are also discovering that there may be other immortal creatures out there. The natural world, from organisms large and small, from jellies to trees to microbes and fungi, likely holds answers that we can’t even conceive of right now. As we discover more biodiversity and as our scientific technology becomes increasingly sophisticated, we are likely to uncover more, which may lead to new avenues for treatments for degenerative diseases and cancer.

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