데이비드 싱클레어, XPrize 대회서 전신 회춘 약물 테스트 계획

EXECUTIVE SUMMARY The outspoken longevity scientist David Sinclair has been predicting that one day, you’ll go to the doctor and get a prescription that will make you 10 years younger. Now MIT Technology Review has learned that he has plans to launch human tests of an oral "reprogramming" drug as part of a $101 million competition organized by the XPrize Foundation. The foundation is offering cash awards to teams able to “restore” a person to an earlier apparent age, as measured by improvements in immune, cognitive, and muscle function. The grand prize goes to any team able to show a 10-year (or greater) relative improvement after one year of treatment. Reached by phone, Sinclair, a biologist at Harvard Medical School, confirmed that he plans to give an oral drug mixture to volunteers in a bid to seek “evidence for age restoration in humans.” The trial, if it goes forward, will be a significant new development in the race to harness so-called epigenetic reprogramming. That technology is based on the discovery, 20 years ago, of powerful genes able to turn an adult cell into a stem cell similar to those found in embryos. The age-reversal effect is believed to occur via a resetting of molecular controls on DNA known as epigenetic marks, which help determine a cell’s overall metabolism and identity. Companies are now racing to use that phenomenon for a new form of rejuvenation medicine. Only this January, one of Sinclair’s companies, Life Biosciences , made news by winning approval to launch an initial human trial using a set of powerful reprogramming genes. The company announced today it had treated its first patient. But that test involves a complex gene therapy and is limited to patients’ eyes, where it could treat conditions like glaucoma. Sinclair’s new plan is bolder: a reprogramming drug you’d swallow in order to promote such effects across the body. “What we’re aiming to do is to epigenetically restore the animal and eventually the person,” he says. “It is true that we’ve been doing extensive animal studies with the oral agent and are looking to compete in the XPrize.” This alternative method, chemical reprogramming, uses drugs to mimic the effects of the embryonic genes. That is significant because drug compounds can travel through the bloodstream, reaching most or all cells in a person’s body. Some experts expressed caution, saying the chemical process, at least as used in labs, is extremely harsh and not even particularly effective. “Who doesn’t dream of whole-body rejuvenation? I think it’s a great goal,” says Sergiy Velychko, founder of Soxogen, a stealth reprogramming company in Boston. “But these chemicals are used in very, very high concentrations for cell reprogramming.” Sinclair declined to describe the exact makeup of the drug candidate, code-named SL-100, calling its contents “highly, highly confidential.” However, he has previously published lab studies of what he called “epigenetic age-reversal cocktails,” which mixed powerful chemicals with known supplements and commercially available medicines. It’s those latter components that would be easiest to test on people, since doctors are free to prescribe them, even for unusual objectives like age reversal. James Clement , head of Betterhumans, an organization that specializes in life-extension studies using existing drugs, said in a message that he is “running clinical trials” of an oral reprogramming cocktail for Sinclair’s XPrize team. Sinclair’s team is competing in the XPrize Healthspan Competition , launched in 2023. It follows several previous competitions that focused on commercial spaceflight, lunar landings, and other goals. The XPrize Foundation is led by executive chairman Peter Diamandis, also an active promoter of longevity research. “If two teams are equivalent, they would split the award,” says Jamie Justice, a doctor and executive director for the contest, which was bankrolled by Saudi Arabia’s Hevolution Foundation, “But it will be incredibly hard to even get to one winner.” Justice says a judging panel is now in the process of picking 10 finalists from 65 teams that have been exploring health foods, lifestyle interventions, digital trackers, and drug compounds. Sinclair’s team, Justice says, was a late entrant to the contest, but like all teams, it would be required to move into wider human tests starting this year. “You have to be ready and in trials,” she says. The race to harness the reprogramming phenomenon and apply it to living people is heating up, even outside the XPrize competition. On June 2, a startup called NewLimit, founded by the crypto billionaire Brian Armstrong, said it had raised a further $435 million , from investors including Peter Thiel’s Founders Fund, to support what it calls “age reprogramming.” The company says it is working toward delivering genetic reprogramming instructions to the liver, to treat diseases of that organ. But Sinclair has been saying that whole-body rejuvenation is a possibility too. And for that, chemicals, rather than gene therapy, could be the most practical strategy. Sinclair says his lab has been searching for such compounds and is starting to use AI “to improve the oral agents that we’re testing.” Chemical reprogramming cocktails, as used in labs, typically involve a mix of vitamins, approved drugs, and experimental molecules. For instance, one recipe Sinclair filed a patent on includes the supplement forskolin, the antidepressant tranylcypromine, and an experimental chemical, laduviglusib, which has been tested against Alzheimer’s, among other ingredients. “In those days it was a six-factor cocktail,” Sinclair says of his earlier research. “But we’ve come a long way. I can’t disclose what's in it, but it’s an improvement and an advance on that, and we’ve done a number of animal studies. They are not published, but we’ve been doing them for a long time, and we want to make sure that we’ve done a full investigation of safety and efficacy before we release any of the data.” While Sinclair’s results aren’t published, other teams say attempts to reverse the age of entire animals using chemical drugs haven’t worked yet. Last year, the lab of Vadim Gladyshev, another Harvard biologist and a member of a different XPrize team, reported on its attempt to rejuvenate mice by installing pumps in their bodies that released controlled doses of seven compounds. Gladyshev says the procedure proved to be toxic . “The idea was to see if we could rejuvenate whole animals. Unfortunately, we have not found [the right] conditions,” he says. “At low concentrations there was no effect, and high concentrations were toxic." Gladyshev says he doesn’t know what is in Sinclair’s cocktail, but says that “trying to improve the combinations makes sense.” Sinclair, who is the author of several books on aging and has a large social media following, has frequently been criticized by other scientists for making unproven rejuvenation claims. In 2024, he resigned as president of the Academy for Health and Lifespan Research after claiming that a supplement developed by a company his brother runs had “reversed” the age of dogs, a claim for which there was so little evidence that one scientist called it a “ lie .” Part of the problem is that scientists still disagree on how to measure aging. And they don’t have a reliable way to measure age reversal, either, should it ever be achieved. Justice, the XPRIZE director, says a primary purpose of the competition is to solve that problem by encouraging the development of standardized measures of aging. That is so that anti-aging drugs can be assessed reliably, and, one-day, approved by regulators if they work. “We as a scientific field have been forced to ask, ‘If a medicine improves how we age, how would we know?” Justice said during a public meeting with FDA officials in May . “If something worked, what would convince us as scientists, what’s meaningful to the general public?” Finalists in the Healthspan competit