Imagine you are visiting a retirement home, talking to people who have lived a long life. A lot of them might have started a family during their lifetime, and are now watching grandchildren grow up. It is always the same order: You are born, you grow up, then you die. Every animal succumbs to this rule. But is that really true?

Out of all creatures we know, a very simple one has managed to trick nature into making it immortal: the tiny jellyfish Turritopsis dohrnii. While immortality sounds surreal and like something that must surely have evolved under extreme conditions, such as the deep sea, this creature can be found, for example, close to Italy. You might have never noticed it when on holiday though, as it is only 3.2 mm large and see-through.

From Medusa to Polyp: A Life in Reverse

So, how does immortality work? T. dohrnii belongs to the taxonomic class of hydrozoans and begins its life as planulae, small free-swimming larvae. These larvae settle down to form a colony of polyps. The form of jellyfish that usually comes to our mind first is also called medusa and buds of these polyps, meaning that each medusa is a clone of the same planula. So far, so normal, as this part of the life cycle is shared with many other jellyfish. What sets them apart is the ability to transform back into a polyp after having reproduced sexually. For humans, this would mean turning back into a baby after having had children!

Genes that Defy Aging

Of course, researchers are fascinated by this unique ability. Understanding it would help enormously with questions about aging and age-related diseases. To do this, you can look at the DNA of the immortal jellyfish and compare it to the DNA of species that cannot rejuvenate. The genomic material in a cell contains all the information needed to keep a cell up and running. It can basically be interpreted as a huge set of instructions, telling the cell what to do. The DNA contains genes, specific stretches of DNA, that each encode one of those instructions. If genes differ between species, the instructions do as well. Finding these differences can give you a hint on how the jellyfish manages to be immortal.

Rejuvenation: Repair and Reset

When it comes to aging, knowing about several cellular processes called the “Hallmarks of Aging”¹ is important. DNA damage makes it more difficult for the cell to follow the instructions they need for survival, and over time they die, which is what we commonly understand as aging. The hallmarks are functions of a cell that are vital for keeping it from accumulating this DNA damage. The genes of T. dohrnii show interesting changes in specifically these functions, implying that the cells are particularly good at repairing their DNA and avoid aging². It was also demonstrated that genes that enable a cell to return to its baby state are kept inactive during the normal life cycle. Only during the rejuvenation process³ are they activated.

Triggers for Rejuvenation

What makes these jellyfish decide that it is time to start anew? Some experiments have suggested that it could for example be caused by stress⁴. If humans would have the same ability, many of us probably would not get far in life before turning back into a baby, given the stressful environment at school, university or work. Another possible trigger could be senescence, a fancy word for the process where cells stop dividing and lose their functional characteristics. This would mean that the cells rejuvenate once they have reached a certain level of biological aging. In both scenarios, rejuvenating makes sense. This way, the jellyfish can regain the abilities of their younger cells and produce many clones that have a chance of escaping the stressor that triggered this process.

Tiny Creatures, Big Secrets

Uncovering the secrets to immortality by studying a tiny jellyfish sounds like the solution to all societal problems related to aging. But as always, things are a little more complicated than they seem. Some changes in genes that could explain the difference in aging between T. dohrnii and other jellyfish could already be identified. Nevertheless, it is still a long way until the precise mechanisms behind this miracle ability are completely understood. Even then, it will be difficult to translate this knowledge to humans and finally to use it to do something about problems that are caused by our cells getting older. This jellyfish shows us that even the tiniest, inconspicuous animals are worth studying and might contain secrets beyond our wildest imagination. Who knows what other special creatures are still out there, with genes that enable them to do things we humans still deem impossible?

Sources

1. López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M. & Kroemer, G. The hallmarks of aging. Cell 153, 1194–1217 (2013).
2. Pascual-Torner, M. et al. Comparative genomics of mortal and immortal cnidarians unveils novel keys behind rejuvenation. Proc. Natl. Acad. Sci. U. S. A. 119, e2118763119 (2022).
3. A decade of transcription factor-mediated reprogramming to pluripotency | Nature Reviews Molecular Cell Biology. https://www.nature.com/article....
4. Schmich, J. et al. Induction of reverse development in two marine Hydrozoans. Int. J. Dev. Biol. 51, 45–56 (2006).