遗传学家探索年龄逆转技术或助恢复视力

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.” 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. As hype around age reversal swirls, Lu has been busy in the lab searching for what he calls “the next generation of rejuvenation therapies.” 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.” “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. 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. 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. 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.”