Why “reprogramming” is the buzziest approach to reversing aging right now
Why “reprogramming” is the buzziest approach to reversing aging right now
为什么“重编程”是目前逆转衰老最热门的方法
EXECUTIVE SUMMARY Earlier this week, Life Biosciences, a biotech company focused on reversing age-related diseases, announced that it had dosed its first volunteer. A person with glaucoma has had an experimental treatment injected straight into their eyeball. The idea is to try to treat the disease—which can cause vision loss—by regenerating healthy nerves in the eye. But David Sinclair, the chairman and cofounder of the company behind the trial, hopes to go further. If the treatment can reverse glaucoma, perhaps similar treatments can reverse other diseases of aging. Maybe, just maybe, they can reverse aging altogether. The approach is designed to work by “reprogramming” cells to a younger state. It’s one of many strategies being explored by biotech companies looking to slow and reverse the process of aging. But of all of them, it seems to be the one that is truly taking off.
执行摘要 本周早些时候，专注于逆转年龄相关疾病的生物技术公司 Life Biosciences 宣布，其首位志愿者已接受给药。一名青光眼患者直接向眼球内注射了一种实验性疗法。该疗法的构想是通过再生眼部健康神经来治疗这种可能导致视力丧失的疾病。但该试验背后的公司董事长兼联合创始人 David Sinclair 希望走得更远。如果这种疗法能逆转青光眼，或许类似的疗法也能逆转其他衰老疾病。也许，仅仅是也许，它们甚至能彻底逆转衰老。这种方法旨在通过将细胞“重编程”回年轻状态来发挥作用。这是生物技术公司为减缓和逆转衰老过程而探索的众多策略之一，但在所有这些策略中，它似乎是目前真正兴起的一种。
Aging is complicated. As we get older, we experience so many changes across pretty much all our biological systems. Scientists have tried to categorize these effects. In 2013, one team published a seminal paper describing nine “hallmarks of aging.” That list features many of the processes scientists have attempted to target. But some of those targets have fallen in and out of fashion over the years.
衰老是复杂的。随着年龄增长，我们几乎所有的生物系统都会经历许多变化。科学家们试图对这些影响进行分类。2013 年，一个研究团队发表了一篇描述“衰老九大标志”的开创性论文。该列表涵盖了科学家们试图针对的许多过程。但多年来，其中一些目标时而流行，时而遇冷。
Take telomere attrition, for example. Telomeres are DNA sequences at the ends of our chromosomes, often likened to the plastic caps that stop the ends of our shoelaces from fraying. When cells divide, telomeres shorten until, eventually, the DNA is vulnerable to damage. When I started reporting on aging, telomere shortening was all the rage. Shrinking telomeres had been linked to age-related diseases of the heart and brain. Shortened telomeres were considered a sign of premature aging. In 2015 Liz Parrish, CEO of the biotech company BioViva, injected herself with an experimental gene therapy that she hoped might lengthen her telomeres. Then it suddenly seemed to go out of style. Research continued, but all the excitement within the aging and longevity community seemed to move on to another hallmark. (Parrish also continued with self-experimentation; she calls herself “the most genetically modified person on Earth.”)
以端粒磨损为例。端粒是染色体末端的 DNA 序列，常被比作防止鞋带末端磨损的塑料帽。当细胞分裂时，端粒会缩短，最终导致 DNA 容易受损。当我刚开始报道衰老领域时，端粒缩短曾风靡一时。端粒萎缩与心脏和大脑的年龄相关疾病有关，端粒缩短被认为是早衰的迹象。2015 年，生物技术公司 BioViva 的首席执行官 Liz Parrish 为自己注射了一种实验性基因疗法，希望以此延长端粒。随后，这一方向似乎突然不再流行。研究仍在继续，但衰老和长寿领域内的兴奋点似乎转移到了另一个标志上。（Parrish 也继续进行自我实验；她称自己为“地球上基因改造程度最高的人”。）
That hallmark was cellular senescence. This happens when cells stop dividing but don’t die, instead entering a “zombie” state in which they churn out chemicals that can cause harmful inflammation. Senescent cells gradually accumulate in pretty much every organ studied, where they are thought to contribute to age-related damage. Why not just periodically clear them out? When a team of scientists took that approach in mice in 2011, they found they could delay the onset of age-related conditions like cataracts and hunchback. The treated mice even looked younger. But when scientists at Unity Biotechnology trialed a similar approach in people with osteoarthritis and an age-related eye condition in the late 2010s and early 2020s, the results were disappointing. The company laid off every employee in May last year and has since shuttered entirely. Again, that doesn’t mean senolytic drugs that target “zombie cells” won’t work. But it feels as if many in the field have moved on.
那个标志就是细胞衰老。当细胞停止分裂但并未死亡，而是进入一种“僵尸”状态时，就会发生这种情况；在这种状态下，它们会产生可能导致有害炎症的化学物质。衰老细胞会逐渐在几乎所有被研究的器官中积累，被认为会导致与年龄相关的损伤。为什么不定期清除它们呢？2011 年，一个科学家团队在小鼠身上采取了这种方法，发现可以延缓白内障和驼背等年龄相关疾病的发生。接受治疗的小鼠看起来甚至更年轻。但在 2010 年代末和 2020 年代初，当 Unity Biotechnology 的科学家在患有骨关节炎和年龄相关眼疾的人群中试验类似方法时，结果却令人失望。该公司去年 5 月解雇了所有员工，此后已彻底倒闭。当然，这并不意味着针对“僵尸细胞”的衰老细胞裂解药物不会奏效，但感觉该领域的许多人已经转向了其他方向。
These days, the buzz is all about ✨reprogramming✨. The idea here is to essentially return cells to a young state. It’s based on the Nobel Prize–winning discovery that four genetic factors can turn an adult cell into a stem cell, which can be encouraged to develop into pretty much any other cell type. Some promising studies in mice suggest that this approach might help wind back the clock. It seems to improve tissue healing, restore vision, and even improve learning and memory.
如今，最热门的话题是✨重编程✨。其核心理念本质上是将细胞恢复到年轻状态。这基于一项诺贝尔奖级的发现：四种遗传因子可以将成年细胞转化为干细胞，进而诱导其发育成几乎任何其他类型的细胞。一些针对小鼠的有前景的研究表明，这种方法可能有助于时光倒流。它似乎能改善组织愈合、恢复视力，甚至提高学习和记忆能力。
Running parallel to all this research are repeated injections of hundreds of millions of dollars in funding. In 2021, my colleague Antonio Regalado reported on the founding of the biotech company Altos Labs to pursue reprogramming for rejuvenation. Altos was funded by the billionaire Yuri Milner—reportedly along with Jeff Bezos, among others—to the tune of $3 billion, a previously unheard of figure for a biotech startup. Other well-funded companies have since sprung up in this space. There’s Retro Biosciences, for instance, which is pursuing reprogramming (among other approaches) in an effort to add 10 years of healthy life to human lifespans. Retro’s launch was supported by $180 million from OpenAI’s Sam Altman. Last month, the company announced a valuation of $1.8 billion. NewLimit, another billionaire-backed biotech exploring reprogramming, says it has promising results from research in mice. It plans to trial a drug designed to rejuvenate the liver in people next year. Last week, the company announced it had raised $435 million toward reaching that goal, among others.
与这些研究并行的是数亿美元资金的持续注入。2021 年，我的同事 Antonio Regalado 报道了生物技术公司 Altos Labs 的成立，该公司旨在追求通过重编程实现返老还童。Altos 获得了亿万富翁 Yuri Milner（据报道还有 Jeff Bezos 等人）的 30 亿美元投资，这在生物技术初创公司中是前所未有的数字。此后，该领域涌现了其他资金雄厚的公司。例如 Retro Biosciences，它正在追求重编程（以及其他方法），旨在为人类寿命增加 10 年的健康生活。Retro 的启动获得了 OpenAI 的 Sam Altman 提供的 1.8 亿美元支持。上个月，该公司宣布估值为 18 亿美元。另一家由亿万富翁支持、探索重编程的生物技术公司 NewLimit 表示，其小鼠研究取得了有希望的结果。它计划明年在人体上试验一种旨在使肝脏恢复活力的药物。上周，该公司宣布已筹集 4.35 亿美元，用于实现这一目标及其他计划。
Life Biosciences, which was founded by the Harvard biologist David Sinclair, most recently secured $80 million to support its research. The eye trial is now officially underway, but Sinclair also has plans for whole-body rejuvenation. Earlier this week, he told my colleague Antonio that he plans to test a “highly, highly confidential” oral reprogramming drug as part of a $101 million competition organized by the XPrize Foundation.
由哈佛生物学家 David Sinclair 创立的 Life Biosciences 最近获得了 8000 万美元的资金支持其研究。眼部试验现已正式启动，但 Sinclair 还有全身回春的计划。本周早些时候，他告诉我的同事 Antonio，他计划测试一种“高度机密”的口服重编程药物，作为 XPrize 基金会组织的 1.01 亿美元竞赛的一部分。
Reprogramming has certainly caught the attention of scientists, biotech companies, and investors. Studies in mice are hugely promising. Human trials are launching. And research in the field has billions of dollars’ worth of support. A lot of people in the field are really excited about reprogramming. But it comes with risks. And we still don’t know if it will work. The question now is: Do we finally have a rejuvenation drug within reach? And if not, what will the next research trend look like?
重编程无疑引起了科学家、生物技术公司和投资者的关注。小鼠研究前景广阔，人体试验正在启动，该领域的研究也获得了数十亿美元的支持。业内许多人对重编程感到非常兴奋，但它也伴随着风险。我们仍然不知道它是否会奏效。现在的问题是：我们终于触手可及地拥有了回春药物吗？如果不是，下一个研究趋势又会是什么？
This article first appeared in The Checkup, MIT Technology Review’s weekly biotech newsletter. To receive it in your inbox every Thursday, and read articles like this first, sign up here.
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