Weight-loss drugs show signs of slowing biological

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.” 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.  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. “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.” 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. “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.” 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. “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.”  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. 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.   “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.” 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.  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.   “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.” 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. 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. 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. “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. “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. 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, but I did not yet see sufficient evidence that they will benefit skinny people,” he said. “I guess we will have to wait.” Answers could start to emerge in a year or two. This past January, a US agency, ARPA-H, put $38 million toward a study in Texas that will attempt to determine whether semaglutide has anti-aging effects in healthy people over 60. That research will look at changes in cognition, mobility, and acuity of the senses. That project also seeks to help define a regulatory pathway for anti-aging drugs and to “build a new therapeutic industry” around longevity.