Axolotls stop aging after four years—could studying them help humans live longer?
The feathery gilled pink salamanders stop aging early and can regenerate their limbs. Studying them could be the next step in the journey to unlocking effective anti-aging treatments in humans.
For humans, aging is inevitable. But axolotls, those cute, smiling amphibians of pop culture fame, seemingly avoid this fate—to a point.
In a phenomenon called neoteny, axolotls never outgrow their larval stage, looking like oversize babies as adults. Not only do they look youthful, with feathery gills and a dorsal fin, these critically endangered Mexican salamanders experience few physical declines and diseases, and can regenerate their limbs, tail, and even organs over their 21-year lifespan.
For that reason, captive-bred axolotls—which are a light pink in color—are common research subjects for biologists, who have long been fascinated by their ability to defy aging. (Learn how you can see wild axolotls in Mexico City.)
Now, a new study unravels one more mystery about these curious creatures. Their bodies stop one of the key mechanisms of aging—the epigenetic clock—when they’re just four years old.
An epigenetic clock estimates an animal’s age based on how life events, such as stress or diet, turns its genes on and off. If an animal has experienced a lot of trauma, for instance, its epigenetic, or biological age, could be much older than its chronological age.
The findings could be one more step in the long quest to discover effective anti-aging therapies for humans, such as reducing inflammation, according to the study published on bioRxiv, a website where studies are posted without peer review. Chasing youth is a popular goal: The anti-aging market, valued at $40 billion, is estimated to hit $60 billion by 2032.
What’s more, understanding axolotl genetics could inspire medicines for regenerating cells, muscles, or maybe even limbs.
“It is a great leap forward in aging and regeneration,” says James Godwin, an immunologist at the MDI Biological Laboratory in Maine who was not involved in the new study. (Read how old age begins later than you might think.)
“If the mechanisms can be understood, then many opportunities to improve human health could present themselves.”
The epigenetic clock
Study co-author Steve Horvath, a geneticist at Altos Labs in California, is an expert in one of the key processes of epigenetics: DNA methylation, which occurs when the body adds and removes chemicals to DNA. These changes then switch genes on and off.
In 2013 he developed an algorithm to look at the pattern of these chemical markers in tissue and correlate them to age, which he dubbed the epigenetic clock. This can consistently predict a person’s lifespan.
To discover what makes axolotls so different from humans, Horvath teamed up with co-author Maximina Yun, a biologist from Germany’s Dresden University of Technology who’s studied the salamanders for years. They created the first-ever axolotl epigenetic clock. (Read how the human body ages rapidly in two bursts, at 44 and 60.)
In Yun’s Dresden lab, the team studied 180 axolotls from four weeks to 21 years of age. Remarkably, the scientists could only create a reliable epigenetic clock for the first four years of an axolotl’s life. After that, the chemical markers simply stayed the same, as if the animals were in a state of arrested development.
“It’s very surprising to the point I can barely believe it,” says Horvath. “To me it’s fascinating that, according to epigenetic changes, axolotls seem to stop aging at four years old.”
State of rejuvenation
The team then built a dual epigenetic clock for axolotls and humans, calculating aging in both species by tracking their DNA methylation.
“The novel thing here is that we’ve developed a clock that can work for humans and axolotls at the same time,” explains Horvath.
This dual clock revealed that axolotls and people age in a similar way, but the amphibians can mysteriously stop the process.
Regeneration could be key, as there seems to be a link between the axolotl’s regenerative powers and the fact it barely ages, the scientists say. (Read how Mexican nuns are working to help wild axolotls.)
In another experiment, DNA analysis revealed that regenerated axolotl limbs are considerably younger than the rest of the animal. In other words, the new tissue essentially reverts to an earlier stage of development.
“We think this could be related to a form of epigenetic rejuvenation,” says Yun. “But this needs more research.”
Potential for human health
The study could also hold new possibilities for regenerative medicine. As embryos, mammals regenerate new tissue after injury instead of repairing wounds with scars, but this capacity is lost with age.
Axolotls, in contrast, regenerate lost tissue throughout their lives. If scientists could understand how, it would advance wound healing, limb regeneration, and amputations.
“Pinpointing the biological events around age four, when the axolotl stops aging, would be critical to replicate [its] regenerative capabilities,” says Virginia Byers Kraus, professor of orthopedics and pathology at Duke University School of Medicine who wasn’t involved with the paper.
What’s more, as people age, our senescent cells, often referred to as zombie cells, stop dividing yet linger in the body, which can lead to inflammation—a risk factor for cancer and other age-related conditions. (Read how inflammation impacts aging.)
Axolotls possess very few of these zombie cells, possibly because of their regenerative abilities. Studying how the axolotl can freeze its development could help researchers find more effective anti-aging treatments for humans—though that would be years down the road.
Overall, the study “gives us hope that if we find out how the axolotl is able to stop the clock,” Yun says, “maybe we can recreate this in other organisms.”
