Naked mole rats, the Church of Perpetual Life, and the quest to discover what the future holds for the human lifespan
Illustration: Zoe Van Dijk
There was a time when San Diego’s Town and Country resort was considered a posh destination. These days, it’s best known for its marquee along Interstate 8, which features one-liners like “There’s no way that everyone was kung fu fighting” and “Welcome archery conference — free ear piercing.”
When I visited in September 2018, the property felt suspended between nostalgia and oblivion. Huge swaths of the late-1960’s-era complex, including the fitness center and hundreds of rooms, were shuttered in preparation for a massive renovation. The areas in operation were decorated with a hodgepodge of kitsch: A large Ron Burgundy poster hung on the wall by the front desk, a flock of plastic lawn flamingos were planted in a patch of artificial turf, and faded pop-art murals painted the elevator doors.
But for the approximately 1,000 people who had paid between $395 and $1,995 to attend the third annual Revolution Against Aging and Death Festival, or RAADfest, the visit to Town and Country was their ticket to a virtually endless future. “We’re on a mission,” James Strole, RAADfest’s fast-talking, silver-haired impresario, told the assembled crowd at the event’s opening ceremony. “We’re creating a new world together — a world without pain, sickness, and death.”
Strole wasn’t speaking hyperbolically. Within the next few decades, he said, it will be normal for people to live for hundreds of years in perfect health. “We’re not talking about life in some decrepit state. We’re talking about life getting better and better and better,” he told his audience, most of whom were already well into their retirement years. “Everybody in this room has that opportunity, no matter what condition you’re in. Your body is miraculous, and it can be turned around.”
Strole was followed onstage by a colorful collection of stem cell cowboys, transhumanists, and robot enthusiasts. The weekend’s biggest draws included Aubrey de Grey, a biogerontologist and anti-death evangelist known for an unruly beard that stretches below his chest and his claim that the first human to live to 1,000 is already living among us; Bill Faloon, a former undertaker who runs a “fellowship for longevity enthusiasts” named the Church of Perpetual Life; and Ray Kurzweil, the inventor and futurist who predicts that we will soon be injecting millions of nanobots into our bodies to fight disease and enhance our cognitive abilities.
The unorthodox cast of characters wasn’t the only reason RAADfest differed from a typical scientific conference. Between three and four hours of every day’s programming was given over to an “anti-aging and age-reversal expo” called RAADcity. Inside, vendors hawked $370 on-site IV infusions of an “all-natural, holistic” vitamin therapy, as well as “youngering” stem cell treatments, lessons in “sex magic,” and something called the Theraphi Plasma System, which claimed to reverse aging, tame children with anger and impulsivity issues, and cure end-stage cancer. One Tampa-based doctor was selling a four-treatment package of “young plasma” for $27,000. Add in a steady stream of amateur song-and-dance numbers and a rambling, free-associative keynote from actress Suzanne Somers and it was tempting to write off RAADfest as nothing but a gathering of kooks, crackpots, and hustlers.
But there were also serious discussions about legitimate, cutting-edge research being conducted at top laboratories and institutes around the world. Faloon, who speaks with the urgency of a door-to-door salesman, enthused about the benefits of NAD+, a co-enzyme with lifespan-extending potential that forms the basis of a new company founded by Leonard Guarente, an MIT professor and aging pioneer. When Kurzweil said he took more than 100 pills and supplements each day, he singled out metformin, a widely used treatment for Type 2 diabetes that prominent longevity researchers believe could treat a range of age-related ailments, including heart disease and cancer. One of the most discussed topics at RAADfest was senolytics, a new class of drugs under development to treat cellular senescence, the scientific term for what happens to our bodies as they deteriorate with age.
“People are fucked up, you know? They’ve been able to trick themselves into thinking that aging is some sort of blessing in disguise.”
This tension between the fringe and the mainstream encapsulates both the dynamic state of aging research and the many open questions about how this research will, in all likelihood, profoundly change the way our species ages in the future. At RAADfest, it is taken for granted that research coming out of established labs across the country will make it possible for humanity to achieve something close to immortality. The prominent scientists who work in those labs, however, overwhelmingly view infinite lifespans as a pipe dream and caution that the interventions they’re working on, while promising, have yet to make humans live longer.
There is nobody who straddles that divide more than de Grey, a 55-year-old British expat who lives in a mountain retreat about 70 miles south of San Francisco. He’s tall and thin, and his ponytail and conspicuous facial hair invite comparisons to Rasputin, the early 20th-century Russian mystic. He’s also a bona fide celebrity in anti-aging circles—when I sat down with him on an outdoor patio during the second morning of RAADfest, our conversation was repeatedly interrupted by admirers who wanted to shake his hand or get his autograph.
De Grey spent the early part of his career as an artificial intelligence researcher and software engineer. When he was 26, he met and eventually married Adelaide Carpenter, a biogeneticist two decades his senior. “Ever since I heard of the concept of aging, it was always obvious that aging was a medical problem and therefore potentially solvable,” he told me as he ran his fingers through his beard. “And so I went through my whole early life just presuming that it was being worked on quite hard by people who were good at that.”
But the more time he spent with Carpenter and her colleagues, the more de Grey became convinced that his presumption was wrong. While technologists like himself were interested in “manipulating nature,” it seemed to de Grey that basic scientists like his wife were content with merely understanding it. (De Grey and Carpenter divorced in 2017; he was at RAADfest with his new fiancée.) “I had never conceived of the possibility that anyone could not think that aging was the world’s worst problem,” he told me. “But when I did, I decided to switch fields.”
It wasn’t long before de Grey was studying aging full-time — with the goal to ultimately cure it. In the 2000s, he helped launch two separate nonprofits to tackle the problem: the Methuselah Foundation, with the motto “to make 90 the new 50 by 2030,” and the Strategies for Engineered Negligible Senescence (SENS) Research Foundation.
De Grey’s mad-scientist appearance and willingness to make bold predictions helped garner attention for his efforts, although it often seemed that the media took him more seriously than the scientific community. After de Grey predicted in 2004 that, within 25 years, scientists would develop “effective rejuvenation therapies for humans,” the MIT Technology Review sponsored a forum into whether SENS was “so wrong that it is unworthy of learned debate.” A few months after that, more than two dozen leading aging researchers published a piece in a peer-reviewed journal that ridiculed de Grey’s approach by quoting H.L. Mencken: “For every complex problem, there is a simple solution, and it is wrong.”
But a decade and a half later, it looks like de Grey might be getting the last laugh: Today, “radical life extension” has entered both the scientific and cultural mainstream, and de Grey’s foundations are awarding grants to some of the most renowned scientists in the field. When I asked him why traditional geroscience researchers were entirely absent from RAADfest’s lineup, he insisted that some of them were “very much on board spiritually with what we do here” but were afraid of offending conservative “mainstream” funders, like the National Institutes of Health and philanthropists “who would rather die than live forever.”
De Grey refers to this as “the pro-aging trance,” which highlights another challenge he faces: In polls, a vast majority of Americans say they would not want medical treatments that slow the aging process and allow people to live decades longer.
“People are fucked up, you know?” he said. “They’ve been able to trick themselves into thinking that aging is some sort of blessing in disguise.”
The Buck Institute for Research on Aging is just off US-101, about 30 miles north of San Francisco. The modernist, I.M. Pei–designed campus borders the Olompali State Historic Park in the foothills of Marin County’s Mount Burdell; groups of deer often graze near its parking lots. When it opened in 1999, the Buck was the first biomedical research institution dedicated solely to aging; today, it is the best funded and most prestigious independent aging research facility in the world. If major advances are made in the fight against aging, it’s likely the Buck will have a hand in them.
In early December 2018, just a few months after RAADfest, I visited the Buck Institute for a daylong symposium titled “Live Better Longer: A Celebration of 30 Years of Research on Aging.” That wasn’t an arbitrary demarcation: Aging is one of the rare areas of modern science with a specific launch date. In this case, it was January 1988, when Tom Johnson, a behavioral geneticist at the University of California, Irvine, published a paper that linked a genetic mutation he named “age-1” to longer lifespans in a transparent, microscopic, mostly hermaphroditic roundworm known in scientific circles as C. elegans.
Prior to Johnson’s discovery, aging had not received a lot of attention from researchers. In the 1820s, Benjamin Gompertz, a self-trained mathematician, concluded that humans don’t start to break down at some magic age but are constantly declining and losing the ability to repair themselves, a concept now referred to as the Gompertz law of mortality. The first hint that there might be a cellular mechanism underlying the aging process came more than a century later, in the 1930s, when two Cornell scientists discovered that rats kept on calorically restricted diets lived significantly longer than their more satiated brethren.
But overall, the field was mostly known as being a haven for charlatans and quacks peddling immortality elixirs and other magical cures — a reputation that continued even after Johnson’s work was published. “In the early 1990s, this was viewed as crazy science,” Valter Longo, director of the University of Southern California’s Longevity Institute, told me. “When people asked, we used to say we worked on something else. We were almost ashamed to say, ‘I work on aging.’”
But over the course of the next decade, the tools of molecular biology began to reveal the inner workings of how lifespan is regulated. In 1993, Cynthia Kenyon, an assistant professor at the University of California, San Francisco, discovered that mutations on a different gene, called daf-2, caused C. elegansto live twice as long as expected. Several years later, Gary Ruvkun, a researcher at Harvard Medical School, showed that these so-called worm-aging genes were closely related to genes in the insulin-signaling system of humans. Around the same time, MIT’s Guarente and some of his colleagues discovered the first of several genes in yeast — which are also present in humans — linked to dramatically extended lifespan.
Johnson, Kenyon, Guarente, and Ruvkun were all part of the opening panel at the Buck symposium, and it was impossible to ignore how much the field had changed. Kenyon, who in 2014 was hired away from her job at UCSF by Calico — the Google-backed biotech company dedicated to combating aging — described her inability to find collaborators, or even grad students, when she was starting out. Guarente recounted the reaction of his department chair when Guarente shared one of his discoveries: “Just what the world needs — long-lived worms.” A few years later, however, one of Guarente’s former postdoctoral researchers sold a pharmaceutical company named Sirtris Pharmaceuticals, which made products based on some of those long-lived worms, to GlaxoSmithKline (GSK) for $720 million.
Ultimately, the Sitris research didn’t pan out, and GSK closed the company, but today, more and more aging-related products are available for consumers. Longo founded a company that sells a five-day fasting-mimicking diet meal kit called Prolon, short for pro-longevity, which his research has linked to changes in biomarkers associated with aging, like inflammation. Guarente told the audience about Elysium Health, a company he helped launch that sells a supplement called Basis, which appears to raise NAD+ levels by up to 40 percent. (The salutary effects of NAD+ were one of the things that Faloon, the Church of Perpetual Life founder, enthused over at RAADfest.) Later on, the president of Unity Biotechnology described his company’s development of senolytics, the class of potentially age-extending drugs that also had everyone at RAADfest buzzing, to treat osteoarthritis, macular degeneration, and pulmonary fibrosis.
Whereas in the past scientists hoped to discover one all-important “aging factor” to target, these days the consensus is that paradigm-changing gains in longevity will come from an all-hands-on-deck approach.
“I think the big success of geroscience drugs will be in their combined action against multiple age-related diseases,” Jan Vijg, a molecular geneticist at the Albert Einstein College of Medicine, told me at Buck. “I think it’s reasonable to predict that maybe three to five years from now, we’ll have a number of drugs based on these little worms that we once thought, well, it’s just an interesting phenomenon.”
Hermaphroditic roundworms aren’t the only unusual animals investigated at Buck for their anti-aging insights. After the day’s second panel, I ducked out of the auditorium to meet up with Rochelle Buffenstein, a native Zimbabwean biologist with strawberry-blond hair, glasses, and a wry sense of humor. While we were having lunch, she told me that her love of food has kept her from adhering to a calorically restricted diet in the hopes of extending lifespan. “I once spoke at a caloric-restriction society meeting and must have looked like the most unlikely person to be there,” she said. “I don’t know if not eating would make me live 20 percent longer, but I’d definitely feel like I was living 50 percent longer.”
Buffenstein has worked as a comparative physiologist in the United States since the late 1990s. After stops at the City College of New York and University of Texas at San Antonio, she was hired by Calico in 2015. When she came out west, Buffenstein brought with her the world’s largest collection of one of the weirdest and most fascinating creatures in existence: the naked mole rat.
Buffenstein keeps her collection of more than 3,500 of the hairless, blind rodents in a series of basement labs at the Buck. Naked mole rats have two massive buck teeth, small holes where their ears should be, and wrinkled, semitranslucent, grayish-pink skin. I’ve been obsessed with them ever since I saw a full-page picture of one as a child, but when I’d visited Buffenstein a year earlier, I hadn’t gotten a chance to visit her animals. (She gave me a naked mole rat plushie as a sort of consolation prize.) Now, after scrubbing my arms up to my elbows and putting on disposable shoe covers and a snood cap, I followed Buffenstein into a tropical walk-in-closet-sized vivarium that housed a colony of several hundred naked mole rats in a series of tubes and clear polycarbonate enclosures that looked like a massive hamster Habitrail.
“Evolution moves by tiny steps, and I think it’s unlikely we’re going to find an intervention that will recapitulate what evolution does,”
Naked mole rats are one of just two eusocial mammal species: Each colony has a single breeding female and a small handful of breeding males. “Lysistrata,” the name of this colony’s breeding female, was written in black ink on a notecard taped to one of the first enclosures in the room. In the wild, naked mole rats live underground, in burrows, and as a result have almost completely lost the ability to regulate their internal temperature, which meant these rooms were kept around 85 degrees Fahrenheit with high humidity.
As soon as we walked in, the animals began chirping. “They have 19 different vocalizations I can recognize,” Buffenstein said before pointing out how the colony designated some of the small, dead-ended enclosures as bathrooms. “They also sometimes eat others’ poop, but only while it is being voided,” she said. (It’s crucial to maintaining a healthy bacteria balance in their gut.) “They really are the most incredible creatures. Do you know they can live for up to 18 minutes without oxygen?”
As amazing as all of that is, the most remarkable thing about naked mole rats — and the reason they are housed at the Buck — is that they seem to have overturned Gompertz’s law of mortality, which is to say their likelihood of dying doesn’t increase as they get older. That doesn’t mean they’re immortal, although a few of Buffenstein’s animals have lived for more than 30 years, roughly 10 times as long as mice and other similarly sized rodents. But naked mole rats, along with Galapagos giant tortoises, rougheye rockfish, ocean quahog clams, and Greenland sharks, are one of a motley crew of creatures that remain active and capable of reproducing right up until they die.
“They maintain heart function, hormone levels — every molecule we’ve looked at in terms of pathways,” Buffenstein said. Put another way: Somehow, even as they get older, naked mole rats don’t seem to age. If Buffenstein can determine exactly how they’re able to do that, the hope is that will help us understand how we might be able to mimic that ability in humans.
With this promising research on the horizon, how long might humans live in the future? Fantastical claims to longevity have existed since the dawn of recorded time, but reliable data about maximum human lifespan only dates to the mid-1950s, when the Guinness Book of World Records began independently verifying claims. Even then, initially corroborated ages can end up disproven: On December 27, a Russian researcher published a paper arguing that the current world record holder, a Frenchwoman named Jeanne Calment, who was reportedly 122 when she died in 1997, had actually passed away in 1934 and had her identity stolen by her daughter.
Assuming Calment wasn’t a fraud, since 1955, 46 people have made it to age 115. Nine of them have made it to 117 — and only two, Calment and an American woman named Sarah Knauss, have made it past 117. (Knauss died in 1999 at age 119). Over that same time frame, just under 11 billion people have been alive. That means roughly .0000004204133 percent of people have made it to 115. You’re 79,333 times more likely to get hit by lightning than you are to live to 115; 22,455 times more likely to end up in the emergency room from a golf cart accident; and 11,817 times more likely to get murdered.
That’s why 115 to 125 is often used as a range for the maximum human lifespan. Some researchers believe that supercentenarians, similar to naked mole rats, are impervious to major age-related diseases like cancer, Parkinson’s, and Alzheimer’s until just before they die. If scientists can figure out how to disrupt the underlying mechanisms that cause our cells to age, the thinking goes, then supercentenarians will become as common as 80-year-olds are today.
Of course, significant challenges remain. Vijg, the Albert Einstein College of Medicine molecular geneticist, emphasizes that researchers still don’t understand the relationship between aging and the diseases associated with it. During a coffee break at the Buck symposium, I asked Vijg, who has a shaved head and an impish smile, what exactly he means. “We define [aging] in very vague terms, like ‘accumulation of damage’ or ‘accumulation of errors in biosynthesis,’ something like that,” he said. “But in fact, we don’t really know what it is. What is the basic mechanism of aging? We don’t know the process.”
Judith Campisi, a Buck scientist and one of the world’s leading senescence researchers, agreed. “Take the 30-fold difference in lifespan between the mouse and the human,” she said. “We don’t understand what it is that makes a mouse age in two to three years and a human age in 50 to 70 or 80 or 90 years.”
“Evolution moves by tiny steps, and I think it’s unlikely we’re going to find an intervention that will recapitulate what evolution does,” she said.
That’s one reason Campisi and Vijg, along with virtually all of the aging scientists I spoke with, think it’s very unlikely that any breakthrough will be able to help us live to 500 — or even to 150, for that matter. “If you’re super, super healthy and you are already going to be a centenarian or a supercentenarian, will those drugs work for you?” Vijg asked me. “Will they now make you live, instead of to 110, will they make you live to 130 or 140? My guess is no.”
Of course, a future where it’s commonplace to live to 110 or 115 would represent a seismic expansion in human lifespan. The speakers and the audience at RAADfest seem to believe that’s the absolute minimum that will result from this esoteric branch of science. The scientists at the Buck symposium, one the other hand, are much cagier about making predictions based on promising initial results. Many of them remember the optimism of the late 1990s and early 2000s, when the initial rash of aging discoveries helped fuel a belief that a “treatment” for aging was just over the horizon.
“It turns out it takes a lot longer to translate from mice to humans than you might expect,” MIT’s Guarente told me toward the end of an hour-long conversation in his office in mid-December. “And we still don’t know for sure that any of this is going to work.”
Update: An earlier version of this story incorrectly stated the stolen identity of Jeanne Calment. It was Calment’s daughter who stole her mother’s identity.