On the afternoon of the 8th, at the animal housing room of the Gene Editing Research Center at the Institute for Basic Science (IBS) headquarters in Daejeon. After entering with a nonwoven cap, mask, gown, latex gloves, and shoe covers covering the whole body, rows of transparent plastic boxes appeared on stainless-steel shelves. Inside boxes thick with white paper bedding, small gray-brown animals, smaller than a palm, moved incessantly. They looked like mice, but the hairless bodies and protruding yellow incisors were unfamiliar.
A super-long-lived animal drawing scientific attention in aging and rejuvenation research settled at IBS last month. It is the naked mole-rat, which Google identified as its first research subject in its bid to unlock the secrets of aging. True to its name, it has no fur and degenerated eyes and looks unimpressive, but it has a lifespan of 32 years, 10 times longer than similarly sized mice. When Google's subsidiary Calico was founded in 2013 and said it would extend human lifespan to 500 years, it did so with confidence in the naked mole-rat.
Naked mole-rats can be seen at three zoos in Korea, but this is the first time they are being raised in a laboratory. There are only a handful of places worldwide that study this animal. Lee Ji-hyeon, a research fellow at the IBS Gene Editing Research Center, said, "It is well known that naked mole-rats live long and are resistant to cancer, but not much has been clarified at the molecular level to establish causality as to why." For that reason, they are regarded in the scientific community as a gold mine for aging and rejuvenation research. Korean science has set out to find a mother lode of healthy longevity that no one has reached.
◇ Make mini organs to track anticancer genes
The naked mole-rat is a unique rodent that lives in the dry tropical savannas of East Africa, including Kenya, Somalia, and Ethiopia. Its body length is 8–10 cm and it weighs 30–35 g. Underground, they live in colonies centered on a dominant female, much like Les Fourmis. The queen mates with several males and gives birth to pups, while the rest are workers without reproductive capacity.
The reason naked mole-rats draw scientific interest is not only their longevity. They do not get cancer and do not feel pain. They can even withstand 18 minutes without oxygen. When oxygen disappears, they can derive energy from fructose instead of glucose. Thanks to that, even hundreds can live underground without suffocating.
The same genes can act completely oppositely to humans. Last year, Chinese scientists reported in Science that an amino acid variation in the naked mole-rat's cGAS protein enhances DNA repair capacity. In humans, this protein promotes cancer, but in the mole-rat, a mutation makes it do the exact opposite. It is as if a troublemaker has turned into a devoted child.
But the reason the IBS team brought in this animal is not to reconfirm its already known "mysterious abilities." The Gene Editing Research Center said it will study the naked mole-rat at the molecular level through genes rather than by visual observation.
Ku Bon-gyung, head of the Gene Editing Research Center, likened this to a radio. To understand how a radio works, you cannot stop at comparing its exterior; you have to "disassemble it and reassemble it." Ku said, "Most naked mole-rat studies so far have focused on comparison, observation, and correlations," adding, "You need genetics to see causality."
The research strategy IBS chose is organoids, known as "mini organs," and gene editing. When stem cells are cultured in three dimensions, they can reproduce the structure and function of real organs. This means they can culture cells for long periods and repeatedly test gene functions without using live naked mole-rats.
The team has already created small-intestine Organoids and plans to establish stomach and liver Organoids next. That will allow confirmation, at the cellular level, of processes for absorbing nutrients and processing waste. The gene scissors, an enzyme complex, can freely cut and paste genes in the Organoid. Observing natural aging takes decades, but such gene editing can induce rapid aging. Comparing this with humans and mice could reveal the much-sought anticancer and longevity genes.
They can also assess anticancer capacity. The team plans to see how naked mole-rat cells respond differently from humans and mice when DNA is damaged. By inducing cancer-causing gene mutations step by step, they can also observe how tumors begin. Lee said, "There is research showing that in naked mole-rats, multiple cancer-related mutations need to be introduced before tumor formation begins," adding, "We want to know what barrier prevents tumor development."
◇ Around-the-clock temperature and humidity control, even a sauna
IBS's naked mole-rat research began last year when three researchers went to the University of Illinois Chicago (UIC) under an international research exchange program and met Professor Thomas Park and Dr. Rochelle Buffenstein, formerly of Calico. Dr. Buffenstein is a leading figure who has studied naked mole-rats her entire life. While at Calico in 2018, she published a striking result in the international journal eLife that naked mole-rats do not age until they die.
Dr. Buffenstein examined the husbandry records of about 3,000 naked mole-rats she had raised over 30 years and confirmed that from six months of age, the daily mortality risk per 10,000 animals remains roughly one case for life, with almost no change. This is regarded as the first confirmation in mammals that the so-called Gompertz law does not apply. According to the 1825 study by British mathematician Benjamin Gompertz, after age 30, a person's risk of death from disease doubles every eight years.
IBS scientists initially went to learn husbandry methods for two weeks to receive a few naked mole-rats for breeding, but as the two were nearing retirement, they donated all 100-plus animals they had, leading IBS to set up a dedicated housing room in just a year. In the meantime, they built, from scratch and one by one, husbandry conditions entirely different from those for other laboratory animals.
Naked mole-rat life is completely different from that of mice. In nature, they connect multiple burrows and set up separate nurseries for pups, food storerooms, and even restrooms. The team connected transparent boxes with pipes to mimic this. Unusually, although they are mammals, naked mole-rats are poikilotherms that cannot regulate their own body temperature. They lack sweat glands and cannot sweat to cool down. They also lack subcutaneous fat and do not tolerate cold well. The team keeps the housing room's temperature and humidity constant around the clock, like underground.
They even set up a sauna. Individuals living in deserts gather in stacks of several layers in burrows close to the ground surface because it is warmer than deep underground. The IBS team laid heating wires like underfloor heating on the bottom of one box. In the housing room, that box was where naked mole-rats gathered most. Lee said, "We call this space the sauna."
Their diet has been localized to Korea. Wild individuals, living underground, mainly eat root vegetables. At the University of Illinois, they were mostly fed sweet potatoes. The IBS team gives domestically grown sweet potatoes, which are much sweeter than in the United States. They also often provide grapes, peaches, and apples. On this day, one animal stood upright, holding a grape in its mouth by the stem, and scratched the wall furiously. Lee explained, "It is instinctive behavior to carry food in its mouth and move it to the storage chamber." They also plan to see how dietary differences change growth.
◇ Accelerating research with an Organoid zoo
Breeding is an even bigger challenge. Even if a male is placed with a queen, they do not mate right away. In some cases, it has taken more than a year to see the first pups in a new colony. If the scent of another colony is present, the queen may kill the male. That is why they keep the animals in separate boxes one to two weeks before mating to let the scent dissipate.
Even distinguishing males from females is difficult by sight, and it is not easy to gauge whether they are sexually mature enough to mate. When a queen disappears, females sometimes engage in life-or-death competition for the position. To prepare for such cases, researchers must frequently check the housing room. To solve these problems, the team said it will develop a method to identify sex via genetic analysis, which until now has been done manually. They also plan to extract stem cells from the testes, where males produce sperm, for research.
The research has not traveled far from the starting line yet. But by viewing the race from a completely different perspective than other runners, the pace is expected to accelerate to a level different from existing studies. The IBS Gene Editing Research Center is building a so-called "Organoid zoo." At the cellular level, they believe they can conduct research comparing multiple animals simultaneously.
The IBS team has created Organoids from stem cells taken from not only laboratory animals and livestock but also wild animals such as bats. Director General Ku said, "We established Organoids for about 20 animal species and submitted a paper to Science, but it was not accepted," adding, "Judging that was not impressive enough, we will resubmit after Chuseok with results from establishing more than 50 species."
One-third of them are birds, which the team said makes them suitable for studying infectious diseases such as avian influenza that affect both humans and birds. The naked mole-rat, the strongest anticancer animal, has also joined the Organoid zoo, enabling comparisons of its anticancer and longevity secrets with other animals.
References
Science (2025), DOI: https://doi.org/10.1126/science.adp5056
eLife (2018), DOI: https://doi.org/10.7554/eLife.31157
Science (2017), DOI: https://doi.org/10.1126/science.aan1505