Jonathan An tries to ignore the hype around new life-extending treatments, but he still gets caught up.
He’s heard the gospel from longevity influencers, including this multimillionaire who has been running a media campaign for months claiming that the 111 pills he takes every day will help him live forever. An, an assistant professor of oral sciences at the University of Washington, doesn’t believe it. But he recently found himself inadvertently caught up in the fervor around anti-aging – thanks to his mice.
An studied mice suffering from periodontal disease, a bacterial inflammatory infection of the gums that can lead to tooth loss. Mice (and more than 60% of adult humans over the age of 65) have to deal with this uncomfortable oral disease – and they have no choice but to deal with it. When teeth fall out, dentists like An replace them. But he would prefer not to have to remove so many.
While studying for his doctorate in dentistry at the University of Washington, An pursued a joint doctorate on research into preventative dental measures. He experimented by giving mice food infused with rapamycin every day to see if it would improve their oral health.
It worked. Mice treated for eight weeks with the drug – traditionally used to help prevent rejection of organ transplants – not only showed delayed symptoms of periodontal disease, but also saw their jaw bones that support the teeth.
This year, An plans to test rapamycin in humans. If it has the same effect in adults as it does in mice, people could eventually get a drug at the pharmacy that would help them avoid unwanted trips to the dentist.
Better dental health would be a nice effect, but that’s not why An’s research has attracted unusual attention. Because the drug An chose to test was rapamycin, the longevity field took note. In separate laboratory experiments over the past decade, rapamycin has been shown to extend the lifespan of yeast, nematodes, fruit flies and mice. It helped mice delay or reverse immune decline, muscle decline, cognitive decline and cancer growth.
This string of successes for rapamycin, which belongs to a class of drugs that silence a biological pathway of cell growth, has attracted the attention of renowned longevity researchers. It has also attracted the attention of wealthy life hackers, clinics, supplement companies, and biotech investors who, out of sincere belief, opportunism, or some combination thereof, seek to make money from people looking for an elixir to live longer.
Since An’s study was published in 2020, longevity clinics across the country have asked him how to incorporate rapamycin into their practices. Some scientists consider rapamycin a good candidate for extending life, both because it has helped laboratory species live longer and because it has already been approved as an immunosuppressant in humans. Today, doctors can and do prescribe rapamycin for off-label use, including for longevity.
An wants to believe that these clinics — part of a burgeoning longevity industry that includes between 50 and 800 providers across the United States, according to the Wall Street Journal — are genuinely trying to improve the health of their clients. But he suspects that’s not always the case.
He tells people about longevity what he knows, which is less exciting than they would hope. As for human health, “I don’t know what rapamycin does,” he said. “But I always tell them to make sure they have a dentist on hand, because some side effects are mouth-related.”
Other companies want him to help with their own studies, the results of which they plan to keep private. An says no. “I’m a dentist,” said An. “Not a salesman.”
A longer, healthier life is one of the easiest products to sell in the world. According to a Deloitte report, the 50 largest longevity companies raised more than $1 billion in venture capital in 2020 – a figure the company said would rise “due to the growing belief that the longevity market longevity could exceed that of existing health care. » Altos Labs, a “rejuvenation” biotech whose investors include Jeff Bezos, announced in 2022 that it had raised $3 billion in funding.
An astronomer’s discovery of a neutron star has much less commercial potential and therefore generates much less interest than a researcher’s discovery that the micronutrient resveratrol helps yeast live longer – even though it is likely that neither ultimately affects human lifespan. The focus on research funded by billionaires risks obscuring whether the field of longevity is truly on the verge of a breakthrough or whether a clinic is simply saying this to promote its experimental blood transfusion.
In reality, research into longevity is progressing, but slowly. Clinical trials are progressing on some uses of longevity drugs, young researchers are taking the field more seriously, and private organizations are pledging significant support for research: the Hevolution Foundation, based in Saudi Arabia, has pledged up to $1 billion. dollars of funding per year for biotechnology startups and university researchers.
But while there likely remain many promising therapeutic candidates that have yet to be identified, getting to clinical trials will take decades. Even academics optimistic about the promise of longevity research worry that, for all the fanfare, the field has become too obsessed with a few drugs and lifestyle adjustments that have been studied for years, while neglecting fundamental research that could reveal new pathways. to slow down human aging.
For now, the three best ways to prolong your life remain boring: eating healthily, exercising regularly, and sleeping well. We’re not going to add decades to human life any time soon; living to be 150 or 200 years old remains the stuff of science fiction. But in the coming decades, advances in the science of aging could yet lead to therapeutic breakthroughs that extend the human lifespan – the period of life spent in good health. Maybe a few more people will become centenarians, but the real success would be having more years where one can live well.
How Longevity Became Common in Academia
Matt Kaeberlein, a longevity researcher at the University of Washington, remembers a time when few academics took the study of aging — much less the idea of longevity — seriously.
“When I came into this field as a graduate student in 1998, no one was going to graduate school to study aging,” he said. “The broader scientific community felt like it was mostly snake oil and bullshit. There’s still a lot of snake oil and bullshit, but it’s more accepted today than before.
The field began to gain recognition in 1993 when Cynthia Kenyon, a pioneer in aging research who now works at Alphabet-owned life sciences company Calico Labs, discovered that mutating a single gene of the roundworm Caenorhabditis elegans doubled its lifespan. Other scientists quickly understood why. Gary Ruvkun, a professor of genetics at Harvard Medical School, and his colleagues found that the modified gene regulated an insulin signaling pathway similar to that in humans, which could play a role in slowing cell growth and metabolism. Researchers like Andrzej Bartke have discovered similar mechanisms in mice, which have so far been the subject of much of the relevant research.
“One of the main things that has happened is that the evidence that you can actually slow down and interfere with the aging process in mammals… has become so overwhelming that only the willfully blind can ignore it,” Richard A. Miller, who heads the University. from the Paul Glenn Center for Research in the Biology of Aging at Michigan, told me.
Over the past two decades, scientists have performed hundreds of laboratory experiments – mostly on animals – on drugs like rapamycin, canagliflozin, acarbose, empagliflozin, metformin, and on interventions like caloric restriction in diets and elimination of senescent, non-dividing cells. Instead of testing the effects of these treatments on specific diseases, many of these studies test whether certain interventions slow down animals’ aging processes and help them live longer.
The expansion of longevity research has uncovered potentially useful information about the biological mechanisms that control aging and how to modify them. In mice and other species, modifying a single pathway has the power to significantly extend life, raising hope that if humans respond in the same way, certain drugs could extend human life by several years.
“We just understand better what these pathways are,” said Tom Rando, director of the Broad Stem Cell Research Center at UCLA, “even if we don’t completely understand why they work and why they extend lifespan.”
Although most experiments with potential drugs for longevity and other interventions like blood transfusions are still tested in laboratory animals, two dozen drug candidates have entered clinical trials in human patients. Daniel Promislow, a professor of medicine and pathology at the University of Washington, told me that when he first got into this field thirty years ago, researchers spoke with hope that early developments would one day come to fruition. laboratory. “Twenty-five or 30 years later, many of these laboratory discoveries are now at the heart of a lot of clinical trials,” he said.
Clinical trials could allow researchers to generate evidence for interventions – beyond diet, exercise and sleep – that could help people live longer. Coleen T. Murphy, a professor of molecular biology at Princeton, wrote in her 2023 book How we age » “What medications can I take to live longer?” » becomes an increasingly tangible objective.
“A few years ago I might have laughed at the naivety of this question,” she wrote, “but now it’s not so crazy to think we’ll be able to take some sort of. ..
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