Weight-loss drugs show signs of slowing biological aging, say drugmakers
Weight-loss drugs show signs of slowing biological aging, say drugmakers
药企称减肥药显示出减缓生物衰老的迹象
Popular weight-loss drugs may do more than help people shed pounds. They might also melt away the years. Drug giants Eli Lilly and Novo Nordisk say patients taking their drugs age less quickly, according to readouts from molecular “aging clocks.” 流行的减肥药可能不仅仅能帮助人们减掉体重，它们或许还能让时光倒流。制药巨头礼来（Eli Lilly）和诺和诺德（Novo Nordisk）表示，根据分子“衰老时钟”的读数显示，服用其药物的患者衰老速度较慢。
Such clocks assess a person’s biological age by looking at changes to DNA that accumulate with time, or, in newer versions, by tracking levels of key proteins. Both companies found that overweight or diabetic patients taking the drugs, called GLP-1s, had reduced biological age compared to those taking a placebo, although the difference varied widely, depending on which type of clock was used, and what organ was tested. 这些时钟通过观察随时间积累的 DNA 变化，或者在较新的版本中通过追踪关键蛋白质的水平，来评估一个人的生物学年龄。两家公司都发现，与服用安慰剂的患者相比，服用这些被称为 GLP-1 药物的超重或糖尿病患者的生物学年龄有所降低，尽管这种差异因所使用的时钟类型和所测试的器官而有很大不同。
Overall, the difference was around “two to three years,” according to Nikolaj Roed, a global project leader at Novo, who says the company has been seeing “improved biological age in our patients across trials and across different tissues.” The findings add to wide speculation among scientists that GLP-1 drugs, as they are known, are acting on basic causes of aging and might be a true longevity treatment. 诺和诺德全球项目负责人 Nikolaj Roed 表示，总体差异约为“两到三年”。他称，公司在各项试验和不同组织中都观察到了“患者生物学年龄的改善”。这些发现加剧了科学界的广泛猜测，即 GLP-1 药物可能作用于衰老的基本成因，并可能成为真正的长寿疗法。
“Two years is a pretty strong effect, in my book,” says Steve Horvath, a professor at the University of California, Los Angeles, who’s credited with inventing aging clocks. Horvath says the emerging data could provide “evidence that these GLP-1 drugs are actually what is known as geroprotectors, medications that slow or possibly even reverse biologic aging.” “在我看来，两年是一个相当显著的效果，”加州大学洛杉矶分校教授、衰老时钟发明者 Steve Horvath 说道。Horvath 表示，这些新出现的数据可能提供“证据，证明这些 GLP-1 药物实际上就是所谓的‘抗衰老保护剂’，即能够减缓甚至可能逆转生物衰老的药物。”
The companies shared their findings over the weekend during Aging Research & Drug Discovery, a conference devoted to seeking scientific remedies for old age. While that quest has not yet produced any clear-cut success, some scientists now think Novo’s drug semaglutide (sold under the names Ozempic and Wegovy) is coming close. 这两家公司在上周末举行的“衰老研究与药物发现”（Aging Research & Drug Discovery）会议上分享了他们的研究结果，该会议致力于寻找针对衰老的科学疗法。虽然这一探索尚未取得明确的成功，但一些科学家现在认为，诺和诺德的司美格鲁肽（以 Ozempic 和 Wegovy 等名称销售）已接近这一目标。
“In an unhealthy population, I do think it’s an anti-aging drug,” says Vadim Gladyshev, a Harvard biologist who assisted Novo with its molecular measurements. “But in a healthy population, no one knows.” “在不健康的群体中，我确实认为它是一种抗衰老药物，”协助诺和诺德进行分子测量的哈佛大学生物学家 Vadim Gladyshev 说，“但在健康人群中，没人知道结果如何。”
The drugs cause weight loss by stimulating a receptor, GLP-1, that tells your brain you’re not hungry. Yet real-world studies have shown much wider benefit. The drugs improve kidney function, reduce blood pressure, and even sharply cut the overall chance of death. 这些药物通过刺激 GLP-1 受体来导致体重减轻，该受体向大脑发出“不饿”的信号。然而，现实世界的研究显示其益处更为广泛。这些药物能改善肾功能、降低血压，甚至大幅降低总体死亡率。
“If the question is, ‘Can semaglutide reach several diseases relevant to health span and aging?’ we know we can say the answer is yes,” said Alejandro Aguayo-Orozco, a senior scientific director at Novo, the Danish drug giant, during the meeting. The next question to answer, he said, is whether such effects are accompanied by changes to molecular measures of biological aging: “When you intervene with semaglutide, does it actually move the clocks in any direction? And the answer is yes.” “如果问题是‘司美格鲁肽能否触及与健康寿命和衰老相关的多种疾病？’我们知道答案是肯定的，”丹麦制药巨头诺和诺德的高级科学总监 Alejandro Aguayo-Orozco 在会上说。他说，下一个需要回答的问题是，这种影响是否伴随着生物衰老分子指标的变化：“当你用司美格鲁肽进行干预时，它是否真的让时钟发生了偏移？答案是肯定的。”
The company found that, over time, the drugs cause a wide slowdown in aging clocks—as much as 4 years in the case of a clock that looks at heart proteins. “I think it’s pretty clear that the organ age is shifting,” said Aguayo-Orozco. 该公司发现，随着时间的推移，这些药物导致衰老时钟出现广泛的减速——在观察心脏蛋白质的时钟案例中，减速幅度高达 4 年。“我认为器官年龄正在发生变化，这一点非常明确，”Aguayo-Orozco 说。
The studies are also a huge boost for the science of aging clocks. Although these measures reflect a person’s age, it’s been uncertain if they are useful as true biomarkers. Now clock makers have evidence that their readouts show a drop in age when people take drugs with broad, well-demonstrated benefits. 这些研究也极大地推动了衰老时钟科学的发展。尽管这些指标反映了一个人的年龄，但它们是否能作为真正的生物标志物一直存在不确定性。现在，时钟开发者们有了证据，证明当人们服用具有广泛且已证实益处的药物时，他们的读数显示出年龄的下降。
“The clock people have been pushing for a decade to get this kind of study done,” says Yuge Ji, a biologist who previously worked in the field and now runs a startup, Reflector Bio. “It’s huge for them.” “时钟研究人员十年来一直致力于推动这类研究，”曾在该领域工作、现经营初创公司 Reflector Bio 的生物学家 Yuge Ji 说，“这对他们来说意义重大。”
As part of its study, Novo took blood draws from 10,052 people, half on the drug and half on a placebo. Their blood, collected at the start of the study as well as months later, was then measured with “proteomic clocks,” which use levels of key proteins to predict a person’s age and risk of dying. 作为研究的一部分，诺和诺德对 10,052 人进行了抽血，其中一半服用药物，另一半服用安慰剂。他们的血液在研究开始时和几个月后被采集，随后通过“蛋白质组学时钟”进行测量，该时钟利用关键蛋白质的水平来预测一个人的年龄和死亡风险。
Scientists at Eli Lilly performed similar research on their GLP-1 drug, tirzepatide, using so-called “epigenetic” clocks that assess age by counting accumulated changes to DNA. Lilly’s study was smaller, but also found that for the most part, molecular time moved more slowly for people on the drug. 礼来的科学家对他们的 GLP-1 药物替尔泊肽（tirzepatide）进行了类似的研究，使用了所谓的“表观遗传”时钟，通过计算 DNA 中积累的变化来评估年龄。礼来的研究规模较小，但也发现，对于大多数服用该药物的人来说，分子时间走得更慢。
“All the clocks are telling a consistent story that we’re seeing a reduction in age,” Kevin Duffin, vice president for aging research at Lilly, said during the conference. “It’s not like we’re going to reverse age by 30 years or something, but it’s a significant reduction.” “所有的时钟都在讲述一个一致的故事，即我们看到了年龄的降低，”礼来衰老研究副总裁 Kevin Duffin 在会上说，“这并不是说我们要逆转 30 年的年龄，但这是一个显著的降低。”
The molecules have become the best selling drugs in the world, with Lilly’s tirzepatide, sold as Mounjaro for diabetes and Zepbound for obesity, topping the list with more than $36 billion in revenue to the company last year. Novo’s semaglutide, also sold under more than one name, was a close second. 这些分子药物已成为世界上最畅销的药物。礼来的替尔泊肽（以 Mounjaro 用于糖尿病和 Zepbound 用于肥胖症销售）去年为公司带来了超过 360 亿美元的收入，位居榜首。诺和诺德的司美格鲁肽（也以多个名称销售）紧随其后。
Alex Zhavoronkov, the founder of Insilico Medicine, and the organizer of the Boston meeting, says that extending lives by even one year across the world’s population would be equal to tens of millions of lifetimes. Last month Zhavoronkov showed that one of his company’s drugs, for a lung disease, also reversed the signals from aging clocks. Insilico Medicine 的创始人、波士顿会议的组织者 Alex Zhavoronkov 表示，如果全球人口的寿命能延长哪怕一年，就相当于增加了数千万个生命周期。上个月，Zhavoronkov 展示了他公司的一种肺病药物也能逆转衰老时钟的信号。
That drug is experimental, but Zhavoronkov has sought to promote the idea that humanity is entering a new era of longevity medicines. He also disclosed during the event that he has been “microdosing” the available weight-loss drugs, even though he is not overweight. 该药物尚处于实验阶段，但 Zhavoronkov 一直致力于推广人类正在进入长寿药物新时代的理念。他还在此次活动中透露，尽管他不超重，但他一直在“微量服用”现有的减肥药。
“I am on tirzepatide and I am an equal-opportunity injector of semaglutide as well,” Zhavoronkov said. It was part of an effort to directly raise the question of whether the first mass-market anti-aging remedy is already here. “我正在服用替尔泊肽，我也同样会注射司美格鲁肽，”Zhavoronkov 说。这是他试图直接提出“首款大众市场抗衰老药物是否已经问世”这一问题的一部分。
“Do you think a reasonable person should start taking semaglutide?” he asked Aguayo-Orozco, the Novo scientist, in front of a crowded audience. “I am not a physician. I cannot answer that question,” Aguayo-Orozco replied. “你认为一个理性的人应该开始服用司美格鲁肽吗？”他在拥挤的听众面前问诺和诺德的科学家 Aguayo-Orozco。“我不是医生，我无法回答这个问题，”Aguayo-Orozco 回答道。
Several people cautioned that GLP-1 drugs do have side effects, including muscle loss. That is one reason they might not help most people, says Horvath, who says he isn’t ready to take the drugs himself, although he’s thought about it. “Clearly, the drugs have many benefits in obese people,” 几位人士提醒说，GLP-1 药物确实有副作用，包括肌肉流失。Horvath 说，这就是它们可能对大多数人没有帮助的原因之一。尽管他考虑过，但他表示自己还没准备好服用这些药物。“显然，这些药物对肥胖人群有很多益处。”