This geneticist’s age-reversal tech could help restore sight

这位遗传学家的逆龄技术有望帮助恢复视力

Yuancheng (Ryan) Lu is obsessed with aging. And with eyes. As he steps outside the Whitehead Institute in Cambridge, Massachusetts, his aviator glasses darken automatically in the sun. Age-related blindness runs in his family. A great-aunt in China, the story goes, was killed crossing a road because she couldn’t see oncoming traffic. And Lu’s own 23andMe test came back with a mutation for macular degeneration, a top cause of vision loss in old age. Exposure to bright sunlight is another risk factor—thus the shades. “They protect me,” he says. “Plus, they look cool.”

陆远成（音译，Ryan Lu）对衰老和眼睛有着近乎痴迷的关注。当他走出位于马萨诸塞州剑桥市的怀特黑德研究所（Whitehead Institute）时，他的飞行员墨镜在阳光下自动变暗。他的家族有与年龄相关的失明史。据传，他的一位姑婆在中国过马路时因看不清来往车辆而遭遇车祸身亡。陆远成自己的 23andMe 基因检测结果显示，他携带黄斑变性的突变基因，这是老年视力丧失的主要原因之一。暴露在强烈的阳光下是另一个风险因素，所以他才戴着墨镜。“它们能保护我，”他说，“而且，它们看起来很酷。”

Lu, 34, works on gene therapies to prevent age-related vision loss. “I think the eye is a really unique system to study aging and rejuvenation,” he says. “I could give a whole presentation.” Pushing up my reading glasses, I lean in to listen. Lu is behind one of the coolest results in rejuvenation science—and in eye research. In 2018, while earning his PhD at Harvard Medical School, he used an age-reversal technique called reprogramming to repair the optic nerves of mice. He crushed the nerves, blinding the animals, and then injected the cells with a gene therapy meant to restore them to a youthful state. Sixteen days later, the nerves were growing back, their axons showing up through a microscope as spidery orange filaments.

34 岁的陆远成致力于研究预防老年视力丧失的基因疗法。“我认为眼睛是研究衰老和复原的一个非常独特的系统，”他说，“我可以就此做一个完整的演讲。”我推了推老花镜，凑近听他讲述。陆远成是复原科学和眼科研究领域最酷成果之一的幕后推手。2018 年，在哈佛医学院攻读博士学位期间，他利用一种名为“重编程”（reprogramming）的逆龄技术修复了小鼠的视神经。他压碎了小鼠的视神经使其失明，然后向细胞注射了一种旨在将其恢复到年轻状态的基因疗法。16 天后，神经开始再生，在显微镜下，它们的轴突呈现出蜘蛛网般的橙色细丝状。

The head of that lab, the longevity scientist David Sinclair, remembers when Lu texted him the pictures: “He asked me, ‘What do you see here?’ And I said, ‘I see the future.’” Later tests carried out in a box with rotating bars of light showed the mice were tracking the changes. They could see again. This year, nearly the exact genetic therapy Lu created for mice entered human clinical trials. On June 9, the startup Life Biosciences, which Sinclair cofounded and in which Lu owns a small stake, announced it had injected the treatment into the eye of a person with glaucoma. The trial has been big news. A headline in the New York Times suggested the technology could “change humanity.” Posters on X gushed, with one declaring that “the fountain of youth is here.”

该实验室负责人、长寿科学家大卫·辛克莱（David Sinclair）还记得陆远成给他发照片时的情景：“他问我：‘你在这里看到了什么？’我说：‘我看到了未来。’”随后在装有旋转光条的箱子中进行的测试显示，小鼠能够追踪光影的变化。它们重获了视力。今年，陆远成为小鼠开发的几乎完全相同的基因疗法进入了人体临床试验阶段。6 月 9 日，由辛克莱共同创立、陆远成持有少量股份的初创公司 Life Biosciences 宣布，已将该疗法注射到一名青光眼患者的眼中。这项试验引起了巨大轰动。《纽约时报》的一篇头条文章称，这项技术可能会“改变人类”。X（原推特）上的用户纷纷赞叹，有人甚至宣称“青春之泉就在这里”。

“It’s remarkable that what he developed as a student is now going into humans,” says Sinclair of the treatment, now called ER-100. “It’s barely even changed since he built it.” Reprogramming refers to an age-restoring process that takes place inside an embryo. It’s why babies are born young, not old: The DNA they’ve inherited from their parents has been scrubbed and reset. In 2006, Japanese researchers showed they could cause the process to occur in the lab by introducing just four key genes, known by the acronym OSKM. Add these to a cell from a 100-year-old and it will turn into a stem cell that acts as if it was plucked from an embryo. That’s powerful stuff.

“他作为学生时开发的技术现在能应用于人体，这非常了不起，”辛克莱在谈到这种现被称为 ER-100 的疗法时说，“自他构建以来，它几乎没有改变。”重编程是指发生在胚胎内部的一种恢复年龄的过程。这就是为什么婴儿出生时是年轻的，而不是衰老的：他们从父母那里继承的 DNA 已经被“擦除”并重置了。2006 年，日本研究人员证明，通过引入四个关键基因（统称为 OSKM），可以在实验室中诱导这一过程。将这些基因加入一个 100 岁老人的细胞中，它就会变成一个干细胞，表现得就像刚从胚胎中取出一样。这非常强大。

But we don’t want to turn people into blobs of stem-cell protoplasm. Lu figured out a way to control the effect. He trimmed the list of genes to just OSK—leaving out M, for Myc, the one most likely to cause dangerous changes like cancer. His extra flash of insight was that reprogramming could be tested on the optic nerve; the eye is particularly accessible. Lu’s result, published in Nature in 2020, helped set off an investment rush. Since then, US tech billionaires have placed huge bets on private companies like Altos Labs and NewLimit to explore reprogramming and anti-aging medicine. The day I spoke with Lu, he’d spent the morning meeting with the business magnate Zhong Shanshan, one of China’s richest people.

但我们并不想把人变成一团干细胞原生质。陆远成找到了一种控制这种效果的方法。他将基因列表精简为 OSK，去掉了 M（即 Myc 基因），因为该基因最容易导致癌症等危险变化。他额外的洞察力在于，重编程可以在视神经上进行测试；眼睛是一个特别容易触及的部位。陆远成的研究成果于 2020 年发表在《自然》杂志上，引发了一股投资热潮。此后，美国科技亿万富翁们向 Altos Labs 和 NewLimit 等私营公司投入巨资，以探索重编程和抗衰老医学。我采访陆远成的那天，他上午刚与中国首富之一、商业大亨钟睒睒会面。

Still, as hype around age reversal swirls, Lu has been notably absent from the public conversation. He’s been busy in the lab searching for what he calls “the next generation of rejuvenation therapies.” With a sigh, Lu describes the grueling effort over the last six years to understand what OSK really does. The treatment remains toxic to many cell types, and he says it’s becoming obvious that different factors drive aging in each kind. This year, for example, he identified a gene responsible for protecting the retina from damage by free radicals—the main cause of age-related macular degeneration.

尽管围绕逆龄技术的炒作甚嚣尘上，但陆远成在公众讨论中却显得格外低调。他一直忙于在实验室寻找他所说的“下一代复原疗法”。陆远成叹了口气，描述了过去六年来为了解 OSK 的真正作用所付出的艰苦努力。这种疗法对许多细胞类型仍具有毒性，他说，显而易见的是，不同类型的细胞由不同的因素驱动衰老。例如，今年他发现了一个负责保护视网膜免受自由基损伤的基因，而自由基正是导致老年性黄斑变性的主要原因。

While Sinclair, his former boss, believes humans could live to be 200, Lu disagrees. There’s just too much that goes wrong as we age. His work with OSK, he says, was more a proof of concept than a silver bullet. But it did change the conversation. “Six years ago, you couldn’t talk about rejuvenation. We didn’t use that word—there was pushback,” Lu tells me. “But I think people have accepted the concept that you can really reverse molecular age.”

虽然他的前老板辛克莱认为人类可以活到 200 岁，但陆远成并不认同。随着年龄增长，人体内会出现太多问题。他说，他关于 OSK 的研究更多是一种概念验证，而非万灵药。但它确实改变了人们的讨论方式。“六年前，你根本不能谈论复原。我们不用这个词——当时有很大的阻力，”陆远成告诉我，“但我认为人们现在已经接受了‘你可以真正逆转分子年龄’这一概念。”