The Naked Mole Rat's Secrets to Immortality

The naked mole rat is finger size, nearly blind, and not particularly cute, even when judged on a rodents-only curve. It also could hold the secret to near immortality: The naked mole rat lives for decades without ever seeming to age. As humanity’s longevity obsession explodes, fostered by an industry expected to surpass $44 billion by 2030, researchers are increasingly focused on the humble naked mole rat’s mysteriously unending youth. While venture capital-backed biotech companies poach top scientists and give them free rein over private labs, the antidotes to all the pitfalls of aging—cancer, heart attack, stroke, cognitive decline—might just be hidden inside this tiny, hairless rodent. More than a hundred labs around the globe are now working with the unusual creatures, and nearly all of the naked mole rats being studied share a single “parent”: Rochelle Buffenstein. She is “the human queen of the mole rat world,” according to Ewan St. John Smith, director of the University of Cambridge’s Naked Mole-Rat Initiative, a lab studying the creatures for their cancer resistance and pain tolerance. In 1987, some of her rats turned seven—a remarkable age for a creature so small. Even 10 years later, her teenage rats were still thriving, leading Buffenstein to apply for a grant to conduct a comparative aging study. In 2002, she published a paper bumping the porcupine from its title of the world’s longest-living rodent. More incredible: Her oldest naked mole rat, a male, had no notable diminishment of muscle mass, bone density, or metabolism. His vascular function stayed strong. That rat lived to be nearly 40, his cause of death a mystery. In the mid-2000s, Google recruited Buffenstein for its newest venture, Calico Life Science, where scientists of all stripes would work to plumb the biology of aging and develop drugs to combat it. They were seeking the fountain of youth, backed by Google’s bottomless budget—and Buffenstein, Queen of the Naked Mole Rat, held a piece of the map. At Calico, Buffenstein studied 7,000 offspring from the rats collected in Kenya. Her creatures showed few to no signs of stroke, neurodegeneration, diminished heart function, or cancer, reinforcing for her that they represented the holy grail of aging. Still, after nearly seven years, she left Calico, convinced that drug development was premature. She gave 6,000 of her critters to other labs and took some 2,000 with her back to academia, where she could focus on persuading naked mole rats to give up their secrets. Today, tucked into a labyrinth of labs at the University of Illinois Chicago, Buffenstein and her colleague Thomas Park oversee the world’s largest naked mole rat collection. Instead of dirt mounds on Kenya’s plains, it exists in rooms hosting nearly 3,000 rodents in colonies of two to over a hundred animals. Each governed by a queen, the colonies live in plastic mouse and rat cages connected by tubing. Creature comforts include a nest, a pantry scattered with gnawed-on yams and corn, and a toilet, where the rats also toss unwanted food and bury their dead. Step into one of Buffenstein’s mole rat rooms and the sound of chirping (each colony has its own dialect) and teeth scraping at cage walls fills the air. In one colony, a mole rat—the colony’s designated bathroom cleaner—balances on its front paws as it furiously kicks excrement into a corner. Naked mole rats are “not the best looking,” admits Buffenstein, but she says they’re “quite cute when you get to know their personalities.” When their cage lids are lifted, dozens of piglike noses point skyward, wildly sniffing the air and showing off four enormous teeth. Some critters are chatty, others violent; some are messy, others clean. There are runners and chewers, escape artists and coup d’etat plotters. The oldest colony, number 3111, is ruled by a 36-year-old queen with a tidy bathroom and a plush paper towel-filled nest all her own. Incredible discoveries come from these plastic abodes filled with endlessly scampering rodents. One key tenet of biology asserts that resources can go either into reproducing or into fighting aging by maintaining a body’s tissues—not both. Buffenstein has found that naked mole rats continue to breed until they die. Females never go through menopause. The queen—the only female to produce offspring in a colony—ages even more slowly than her subjects. That fountain of bucktoothed youth even extends to the naked mole rat’s particular beauty. Buffenstein’s research has shown that as the years tick by, naked mole rats maintain juvenile—even fetal—biological features inside and out. She plucks one, a male, from his colony. “Hey, gorgeous,” she coos, before placing him in a small box with tubes pumping in a vaporized anesthetic. Her research is currently focused on the heart and the brain: cardiac disease and neurodegeneration. This, she believes, is where naked mole rats hold the secret to their longevity. Human hearts begin to decline at age 17. Even at twice that age, the naked mole rat doesn’t show any reduced heart function. In the lab, Buffenstein waits for the critter to go under so she can perform an ultrasound, but she runs into a complication. Naked mole rats can survive for 18 minutes without oxygen and show no related effects afterward. Even understanding this one talent could unlock treatments for long-term damage from strokes and heart attacks in humans. But right now, the rat’s superpower is a pain. Five minutes have passed and he’s still scampering around. “He’s holding his breath,” Buffenstein says. The anesthetic is useless against the wrinkly pink Houdini. She finally gives up. Back in Buffenstein’s office—where the curtains, throw blankets, and mugs all wear her rats’ toothy expressions—she flips her computer open to a PowerPoint presentation. On one slide she’s compared two of the oldest people in known history: A French woman who smoked two packs of cigarettes a day nearly until her death at age 122 and a Cape Town resident who set the record for the fastest 100-meter sprint by a centenarian (30.86 seconds). They seem to illustrate all that we don’t know: Why do some people live so long, and remain so physically hale? Is it nature, or nurture, or something else? Buffenstein believes there’s no point in living longer if it doesn’t come with an equal extension of our health, and all her research asks one big question: How do naked mole rats avoid the perils of aging so well? Their hearts, muscles, digestion, reproduction—none seem to degrade. Do they have one secret, or is it a thousand small genetic details adding up to a more perfect system? The answer, she believes, could change our ability to stay younger longer, at a cellular level. “If we could figure out what it was and mimic it in human medicines, maybe we could improve our health span too,” she says. Of course, Buffenstein isn’t the only researcher trying to charm naked mole rats into giving us answers. A Japanese lab recently discovered the system by which naked mole rats purge problematic cells, preventing age-related damage. In Germany, scientists realized that the rats barely respond to heat-based pain on their skin, including that caused by acid. Cambridge researchers have revealed how the animals’ immune system stops cancerous cells from developing into tumors. “In 10 years I think we’ll already have some treatments for humans based on what was discovered in naked mole rats,” says Vera Gorbunova, co-director of the Rochester Aging Research Center in New York. Gorbunova is helping chart that path by exploring the rats’ ability to effectively cure cancer before it can take root. She’s homed in on the rats’ heightened production of hyaluronan, a sugar that lives in tissue and seems to suppress their cancerous tumors. Humans make less hyaluronan, and it degrades faster in our bodies. Gorbunova reasons that if we can slow the degradation, we could also slow how cancer metastasizes. In 2023, her lab successfully engineered just that in mice. Now, she and her team are moving toward drug discovery. “In this case we used it against cancer,” Gorbunova says. “At some point we can see if it helps to slow aging.” And yet, even breakthroughs like Gorbunova’s leave one fundamental mystery unsolved: Does the naked mole rat age slowly, or does it simply not age? At one time, scientists leaned toward option B. In a 2021 study, Buffenstein wrote that “death and disease both appear to be stochastic and independent of chronological age” in naked mole rats, and therefore they could—at least, until their 30s—“be classified as a ‘non-ageing’ mammal.” For geneticist and biostatistician Steve Horvath, that would have made the naked mole rat his white whale. In 2013, while at UCLA, he invented a method dubbed the epigenetic clock, used to test biomarkers of aging in our cells. He’s long searched for a mammal that shows what scientists call negligible senescence—aka agelessness. “Everyone thought it was going to be the naked mole rat,” he says. But when he collected hundreds of naked mole rat tissue and organ samples for testing, what he found was disappointing—and incredible. At a molecular level, the naked mole rat does age. It’s just that, along the way, the rat’s biology resisted nearly every ailment mammals—particularly humans—suffer from as they get older. Buffenstein sees the proof in the raw numbers: Over four decades spent studying thousands and thousands of naked mole rats, only 10 of hers have succumbed to cancer. When asked what most naked mole rats do die of, she throws her hands up. “That’s the million-dollar question!”