David Sinclair plans to test whole-body rejuvenation drugs in the XPrize competition
David Sinclair plans to test whole-body rejuvenation drugs in the XPrize competition
大卫·辛克莱计划在 XPrize 竞赛中测试全身回春药物
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. 执行摘要 直言不讳的长寿科学家大卫·辛克莱（David Sinclair）一直预言，总有一天，你去医院看病时会拿到一张能让你年轻 10 岁的处方。据《麻省理工科技评论》获悉，他计划作为 XPrize 基金会组织的 1.01 亿美元竞赛的一部分，启动一种口服“重编程”药物的人体试验。
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. 该基金会向那些能够使人“恢复”到更年轻生理状态的团队提供现金奖励，衡量标准是免疫、认知和肌肉功能的改善。大奖将颁发给任何能在一年治疗后表现出 10 年（或以上）相对改善的团队。
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. 哈佛医学院生物学家辛克莱在电话中证实，他计划向志愿者提供一种口服药物混合物，旨在寻求“人类年龄逆转的证据”。如果这项试验得以推进，将成为利用所谓“表观遗传重编程”技术竞赛中的一项重大进展。
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. 这项技术基于 20 年前的一项发现：某些强大的基因能够将成年细胞转化为类似于胚胎中的干细胞。人们认为，年龄逆转效应是通过重置 DNA 上的分子控制（即表观遗传标记）来实现的，这些标记有助于决定细胞的整体代谢和身份。
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. 目前，各家公司正竞相利用这一现象开发新型回春药物。就在今年 1 月，辛克莱旗下的 Life Biosciences 公司因获批启动一项使用强效重编程基因的人体初步试验而登上新闻。该公司今日宣布已治疗了首位患者。
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. 但该试验涉及复杂的基因疗法，且仅限于患者眼部，旨在治疗青光眼等疾病。辛克莱的新计划更为大胆：开发一种可以通过吞服来促进全身此类效果的重编程药物。
“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.” “我们的目标是通过表观遗传学手段恢复动物，并最终恢复人类的生理状态，”他说。“我们确实一直在用这种口服制剂进行广泛的动物研究，并计划参加 XPrize 竞赛。”
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. 这种替代方法——化学重编程，利用药物来模拟胚胎基因的效果。这一点意义重大，因为药物化合物可以通过血液循环，到达人体内的大部分或全部细胞。
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.” 一些专家对此表示谨慎，称这种化学过程（至少在实验室中）极其严苛，甚至效果并不显著。波士顿隐形重编程公司 Soxogen 的创始人谢尔盖·维利奇科（Sergiy Velychko）表示：“谁不梦想全身回春呢？我认为这是一个伟大的目标。但这些化学物质在细胞重编程中使用的浓度非常、非常高。”
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. 辛克莱拒绝透露代号为 SL-100 的候选药物的具体成分，称其内容“高度、高度机密”。然而，他此前曾发表过关于他所谓的“表观遗传年龄逆转鸡尾酒”的实验室研究，其中混合了强效化学物质、已知补充剂和市售药物。
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. 正是这些后一类成分最容易在人体上进行测试，因为医生可以自由开具处方，即使是为了年龄逆转这种不同寻常的目标。专门研究利用现有药物延长寿命的机构 Betterhumans 的负责人詹姆斯·克莱门特（James Clement）在信息中表示，他正在为辛克莱的 XPrize 团队“进行临床试验”，测试一种口服重编程鸡尾酒。
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. 辛克莱的团队正在参加 2023 年启动的 XPrize 健康寿命竞赛（Healthspan Competition）。此前，该基金会曾举办过多次针对商业航天、登月等目标的竞赛。XPrize 基金会由执行主席彼得·迪亚曼迪斯（Peter Diamandis）领导，他也是长寿研究的积极推动者。
“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.” “如果两支团队表现相当，他们将平分奖金，”该竞赛的执行董事、医生杰米·贾斯蒂斯（Jamie Justice）表示。该竞赛由沙特阿拉伯的 Hevolution 基金会资助，“但要产生一个获胜者将极其困难。”
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. 贾斯蒂斯表示，评审团目前正在从 65 支探索健康食品、生活方式干预、数字追踪器和药物化合物的团队中挑选 10 支决赛入围者。贾斯蒂斯说，辛克莱的团队是竞赛的后期加入者，但像所有团队一样，他们必须从今年开始进入更大规模的人体试验。“你必须做好准备并进入试验阶段，”她说。
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.” 利用重编程现象并将其应用于活人的竞赛正在升温，即使在 XPrize 竞赛之外也是如此。6 月 2 日，由加密货币亿万富翁布莱恩·阿姆斯特朗（Brian Armstrong）创立的初创公司 NewLimit 表示，已从包括彼得·蒂尔（Peter Thiel）的 Founders Fund 在内的投资者那里额外筹集了 4.35 亿美元，以支持其所谓的“年龄重编程”。
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. 该公司表示，正致力于将基因重编程指令传递到肝脏，以治疗该器官的疾病。但辛克莱一直表示，全身回春也是一种可能。对于这一点，化学物质而非基因疗法可能是最实用的策略。
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. 辛克莱表示，他的实验室一直在寻找此类化合物，并开始使用人工智能“来改进我们正在测试的口服制剂”。实验室中使用的化学重编程鸡尾酒通常涉及维生素、获批药物和实验性分子的混合物。
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. 例如，辛克莱申请专利的一项配方中包括补充剂毛喉素（forskolin）、抗抑郁药反苯环丙胺（tranylcypromine）以及一种曾用于阿尔茨海默病测试的实验性化学物质 laduviglusib 等成分。
“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 [it].” “在当时，那是一种六因子鸡尾酒，”辛克莱在谈到他早期的研究时说。“但我们已经取得了长足的进步。我不能透露其中的成分，但它是在此基础上的改进和提升，我们已经进行了多次动物研究。这些研究尚未发表，但我们已经进行了很长时间，我们希望在发布任何（相关成果）之前，确保我们已经对安全性和有效性进行了充分的调查。”