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A 2024 review published in the Spanish academic outlet Revista Española de Geriatría y Gerontología examined how this process works and what it could teach researchers about regeneration and human aging.
The researchers focused on a process called transdifferentiation, in which a mature cell changes into a different type of cell. Their review found that the jellyfish’s ability to rejuvenate is linked to major changes in its cells, genes, DNA repair systems and mechanisms that maintain the ends of its chromosomes.
How does the immortal jellyfish reverse its life cycle?
Turritopsis dohrnii normally begins its life as a polyp. The polyp develops into a medusa, the free-swimming form we recognize as a jellyfish. But the species has another option.
When the mature jellyfish experiences damage, aging or environmental stress, it can transform into a cyst-like stage and then return to what the researchers describe as a reversed polyp. That polyp can later develop into a new jellyfish. In simple terms, the animal can move backward in its life cycle and start again.
This is why it is known as the immortal jellyfish. The name does not mean the animal cannot die. Predators, disease and other external threats can still kill it. Its unusual ability is to reverse its development under certain conditions.
The cellular process behind the reset
The researchers looked closely at transdifferentiation, the process that allows cells to change their identity. Unlike ordinary development, where cells become increasingly specialized, transdifferentiation gives certain mature cells the ability to change into another cellular identity.
The review suggests that this cellular flexibility plays an important role when T. dohrnii reverses its life cycle.
Scientists compared gene activity at different stages of the jellyfish’s development and found major differences when it entered its cyst stage.
Genes involved in DNA synthesis, DNA repair, nucleic acid metabolism and telomere maintenance became more active.
At the same time, genes involved in some forms of cellular communication and signaling became less active.
The researchers also found changes in the Wnt and Notch pathways, which are involved in processes such as development, cell positioning and organ formation.
The pattern suggests that the jellyfish places a strong emphasis on maintaining and protecting its DNA during its cellular reset.
The jellyfish appears to prioritize DNA protection
Several genes discussed in the review are linked to DNA maintenance. These include POLD1 and POLA2, which are involved in DNA replication, as well as TOP3B and GEN1, which are involved in DNA-related processes. The review also discusses BRCA1, a gene associated with tumor suppression.
Other molecular mechanisms appear to help protect the jellyfish from oxidative stress and DNA damage. This is important because cellular reprogramming can be risky. Cells need to change their identity while keeping their genetic material stable.
The researchers suggest that in T. dohrnii, maintaining DNA quality appears to take priority over rapid cell division during the regenerative stage.
Telomeres may also play a role
The review also examined telomeres, protective structures at the ends of chromosomes that shorten or become dysfunctional as cells age. T. dohrnii has genetic features associated with telomere maintenance. The researchers highlighted multiple copies of the GAR1 gene, which is part of the telomerase complex, as well as variants of POT1, a gene that regulates telomeres.
The jellyfish also has a duplicated GLI3 gene associated with stem-cell function.
Together, these findings suggest that the jellyfish has several mechanisms that help preserve cellular function during its remarkable transformation.
Humans can reprogram cells too but there is a catch
The jellyfish’s biology is interesting to human aging researchers because humans also have ways of reprogramming cells.
Scientists have experimentally converted mature human cells into different types, including heart cells, neurons and pancreatic beta cells.
But there is a major difference. In humans, cellular reprogramming can also increase the risk of oncogenic activity, meaning processes associated with cancer. The review links this risk to problems including DNA damage, oxidative stress and telomere dysfunction.
As humans age, reactive oxygen species can accumulate and damage cells and DNA. Changes in telomeres and other cellular systems can further affect how cells behave.
So while cellular reprogramming can potentially help repair tissues, doing it safely remains a major challenge.
What does the jellyfish mean for human aging?
The review does not show that humans can reverse aging by copying the jellyfish. Instead, T. dohrnii provides scientists with a natural example of an organism that can rejuvenate through cellular reprogramming.
Understanding how it protects its DNA, maintains telomeres and controls changes in cell identity could eventually help researchers develop safer regenerative treatments.
The authors suggest that future research could explore whether lessons from jellyfish might inform treatments for age-related and chronic diseases, including dementia and cancer.
