Groundbreaking experiment ‘exports’ longer life into supermice from naked mole-rat genes

A mouse lives about three years. A hamster, four. A gray rat, five. A guinea pig, 12. A capybara, 15. And an eastern gray squirrel, 24. They are all rodents and distant cousins, some are even similar in size, but the staggering differences in their lifespans suggest that the longest-living ones hold the secret to longer, healthier lives. When it comes to life expectancy, the naked mole-rat (Heterocephalus glaber) breaks all records. This animal lives in underground colonies in the Horn of Africa. It is the size of a mouse, but it lives for around 30 years, and some specimens even live beyond 40. On Wednesday, a team led by biologist Vera Gorbunova announced that they had managed to “export” this incredible longevity to another species. The scientists achieved this by inserting a gene from the naked mole-rat into mice, creating supermice that live longer and are more resistant to cancer.

Gorbunova, the co-director of the Rochester Aging Research (RoAR) Center in the United States, believes that the results show that the mechanisms of long-living animals can be exported to humans. Six years ago, at a conference in Madrid, the biologist showed a photograph of the 1546 painting The Fountain of Youth, painted by German artist Lucas Cranach the Elder. In the oil painting, the elderly and the sick emerge rejuvenated from a pool with miraculous waters. “My job is to find the fountain of youth,” Gorbunova told the conference. Her new results are “a part” of that fountain, she now says.

The naked mole-rat is a puzzling animal. It can live up to 40 years without getting cancer or other diseases related to aging, such as arthritis and cardiovascular and neurodegenerative disorders. A decade ago, Gorbunova’s team discovered a cause for the animal’s unusual resistance to tumors: its cells produce hyaluronic acid, which is over five times stronger than that produced by humans or mice. This extremely high-molecular-mass hyaluronan (HA) — a long sugar polymer — has anti-inflammatory and anti-cancer properties.

In the study, Gorbunova’s team inserted the gene that produces this extraordinary hyaluronic acid into about 90 mice. The resulting mice lived 4.4% longer on average, with a 12% increase in maximum life span. In a similar group of mice that did not receive the gene, the incidence of cancer reached 83% in old age, compared to 49% in the genetically modified mice. “This is the first time that a mechanism of this type has been successfully exported,” says Gorbunova.

Aging expert Pura Muñoz has welcomed the new research, which was published Wednesday in the journal Nature. “The resulting mouse is fabulous in many ways, a true super mouse. They live much longer than their species should, which is related to a lower level of inflammation and a greater protection of the intestinal barrier with age. It is better equipped to resist the stress of the passage of time,” she explains.

Muñoz works for Altos Labs, a U.S. multinational dedicated to enabling humans to live longer, healthier lives. The company, founded in 2022, has an astounding $2.5 billion budget, and four Nobel laureates on the payroll. “This is the first work that shows that the transfer of a characteristic of a species with a long lifespan to another species with a much shorter lifespan is capable of lengthening life, with signs of healthier aging,” Muñoz explains

Gorbunova — who was born in St. Petersburg, in the former Soviet Union — is already looking for strategies to safely increase HA levels in people. “Transgenesis could be done, administering the [naked mole-rat] genes into adult human tissues using vectors [viruses, for example] or nanoparticles. The best option, of course, would be to use small molecules to avoid the degradation of the high-molecular-mass hyaluronan,” she explains.

Her supermice lived up to 12% longer in the experiment, but that number pales in comparison to what is observed in nature. Naked mole-rats live 1,000% longer than mice. Gorbunova explains that her genetically modified mice synthesize much more hyaluronic acid, but they also break it down at a fast rate, unlike naked mole-rats, which accumulate it. The biologist says that her laboratory is already testing experimental drugs that reduce this natural degradation.

Venezuelan biologist Jorge Azpurua studied the anticancer properties of HA in naked mole-rats a decade ago in Gorbunova’s laboratory. “The new results are very interesting. The question 10 years ago was whether high-molecular-mass hyaluronan was enough to reduce the risk of cancer, or whether there were multiple molecular mechanisms involved. From what I see in this work, it is enough,” says Azpurua, who is now focused on breast cancer research at George Washington University, in the United States.

Azpurua also warns against drawing hasty conclusions. “We have to be prudent, because the molecular biology of rodents, in general, is quite different from that of human beings. The most important thing, in my opinion, would be to try to understand the molecular mechanism through which hyaluronic acid reduces the incidence of cancer,” he says.

At the moment, there is still no elixir of eternal youth. High-molecular-mass hyaluronan, in fact, is associated with inflammation and cancer metastasis, the authors of the study point out. In a 2022 study, biologist Esther Titos, from the Clínic Hospital in Barcelona, showed that people with obesity have high levels of low molecular weight hyaluronan, which promotes inflammation and metabolic diseases. For Titos, the new results are “spectacular,” but she also calls for caution. “Nobody should run to the pharmacies to eat gels with hyaluronic acid,” she jokes.

For decades, this injected sugar has been used to treat various disorders, such as osteoarthritis and chronic wounds that fail to heal. But there are doubts about whether this treatment is really beneficial. It is also used in aesthetic medicine, for example, in procedures to hide nose asymmetries, but again there are doubts about its efficacy and safety. In the world of cosmetics, it is a very common ingredient. “Many doors are now open to research the mechanisms, but we should not jump on the idea that high-molecular-mass hyaluronan extends life. It is a study in mice; we must be cautious,” says Titos.

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