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Axolotls have been receiving quite the spotlight as of late. These charming amphibians have become popular exotic pets on account of their unique appearance and lifestyle. Despite the recent surge of interest in these fascinating creatures, few people know that their impact on humanity may well extend beyond serving as an unorthodox animal companion. As it turns out, axolotls are one of the few vertebrates that maintain a lifelong ability to significantly regenerate lost tissue. Enterprising scientists have fixed their eyes on this talent in the hopes that we might someday be able to imitate it in human medicine.
Before we jump into that research, it’s wise to cover some basics of axolotl biology. Despite their unusual appearances, axolotls are actually a type of salamander. What makes them different from their more lizard-like cousins is the fact that they are neotenous—they retain “adolescent” salamander characteristics throughout their entire lives. If you were to look at a picture of a juvenile tiger salamander, for example, you would find that it looks remarkably similar to an axolotl—feathery external gills, finned tail, and all:
[Life stages of the tiger salamander, Ambystoma mavortium. Public Domain. See on Wikipedia.]
These characteristics simply disappear as the salamander matures and gains the structures necessary to be able to venture onto land. Axolotls, perhaps due to the isolated environment in which they are naturally found, have lost the ability to metamorphose into an “adult” salamander form.* They essentially spend their whole lives in a “juvenile” body plan. Though this does come with some downsides, like being unable to leave the water, it also may be the reason that they resist many symptoms of aging and retain heightened regenerative abilities throughout their lives.
Regeneration isn’t a skill unique to axolotls. In fact, every living organism is capable of regeneration to some degree. The process of cellular division in our skin, for example, is regenerative—it allows missing or damaged tissue to be replaced. What’s unique about axolotls is that, compared to other vertebrates, they have an immense ability to regenerate. Like other salamanders, they have the ability to completely regenerate lost limbs. They can also regenerate organs and even parts of their brains, something that is unprecedented in the animal kingdom. When they are wounded, they don’t form scars. They form seamless new tissue, as though the wound never existed. The way they accomplish this feat is just as impressive as the act itself. When an axolotl must regenerate missing tissue, its body accomplishes the task by instructing surrounding cells to un-differentiate, returning to something akin to stem cells. These undifferentiated cells aren’t able to transform into any cell type like a true stem cell, but they are readily able to re-form into the same type of cell they were before. Using the same developmental pathways that helped form the missing part initially, an axolotl’s body can coordinate these flexible cells as they replicate and reorganize. The end result is a perfectly functional new limb, organ, or section of the brain—down to the organization of neuron connections and blood vessels.
This skill, plus their presence in the pet market, makes them excellent models for research into the nature of regeneration. In particular, scientists are eager to see whether their regenerative abilities can somehow be ported over to humans. The complete mapping of the axolotl genome in 2018 helped crack open the case, allowing researchers to uncover crucial genes in the regulation of tissue formation and regeneration. By finding comparable genes (analogs) in the human genetic code, researchers hope to someday find a way to harness the axolotl’s regenerative powers for human benefit using techniques such as gene therapy. The way we currently heal our wounds—by forming scars—can be harmful in many cases. Scars are tough and inflexible, leaving the door open for pain and loss of mobility. If dormant or suppressed genes surrounding tissue regeneration in humans could somehow be activated, it might be possible to prompt wounds to heal by reforming the tissue in its original state—skipping all the hangups of traditional scars. As technology further progresses and scientists come to better understand the other factors that play a role in guiding regeneration in axolotls, some even hope that we may be able to unlock the ability to fully regenerate our own limbs. There’s also a chance that regeneration technology may prove useful in combating age-related mental conditions like Alzheimer’s. Axolotls are able to repair lost neural connections in the brain through regeneration; in humans, where the loss of neural connections is more or less permanent, this kind of healing would be groundbreaking.
Research into the applications of axolotl regeneration in human medicine is only just starting to pick up steam, and it’s likely that further developments in this area will surface in the near future. If you’ve been looking for a new STEM subject to keep your eyes on, the humble axolotl may be an ideal choice!
* Metamorphosis isn’t completely impossible for axolotls. Some axolotls have mutated back into the ability to metamorphose, and metamorphosis can be induced with certain hormones. In the case that they do metamorphose, they resemble any other adult salamander.
References & Further Reading
Though this article is a bit on the older side, it does a great job of comprehensively covering the amazing abilities of the axolotl. If you're interested in getting a baseline on axolotl regeneration and the many other fascinating quirks that come from the species' neoteny, this is a great place to start!
This brief YouTube video is another great place to look for baseline information on axolotls. It offers some historical context on the axolotl species, plus an interview with an axolotl researcher and time-lapse footage of axolotl regeneration.
This article from Harvard's "Science in the News" blog does a great job of explaining the mechanics of axolotl regeneration and their potential for the future of human medicine.
This scientific journal article from 2019 does a great job of summarizing recent discoveries in axolotl biology. If you're interested in an academic deep dive with plenty of further resources to explore, this article is the perfect place to look!
This source offers a researcher's perspective on some of the most recent axolotl research. It discusses the amazing ability of an axolotl to regenerate neural connections in its brain, and it offers a wide variety of links to further sources for those interested in learning more!
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