GLP-1 weight-loss drugs are transformational. From helping people lose weight to controlling their blood sugar to tamping down inflammation and improving heart health, these medications herald a new age of medicine. And now a new study in mice suggests that starting semaglutide, a GLP-1 (glucagonlike peptide 1) medication sold under the brand names Wegovy and Ozempic, in old age extends the lifespan by about 12 percent.
Not only that, but semaglutide outperformed dieting in terms of maintaining memory and keeping blood sugar in check. It’s an intriguing result: Scientists already knew that restricting calories seems to boost longevity and hold off the ill effects of aging. But sticking to such a diet is hard, and researchers have long looked for a drug that delivers the same benefits without the hunger. The new results, published in Nature, suggest they may have found it.
In the study, scientists gave semaglutide to female mice that were 20 months old—roughly equivalent in age to a woman in her 60s—and injected them with the drug for the rest of their lives. Against a comparison group of the same age that ate freely and received only saline shots, the mice’s median lifespan rose by about 12 percent—from 742 days to 834.
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Semaglutide’s list of uses has grown long in recent years. Beyond being used to treat diabetes and obesity, it is approved to lower cardiovascular risk, slow kidney decline and treat fatty liver disease, with trial data piling up for sleep apnea and osteoarthritis. Why one drug works in so many seemingly unrelated conditions is a mystery. “I read in journals about all these benefits for all kinds of diseases, and I don’t think there was an answer in the scientific community,” says Danica Chen, a longevity researcher at the University of California, Berkeley, and senior author of the new study.
Chen has researched calorie restriction for two decades and thought that semaglutide might work as a dieting substitute because it also reduces calorie intake, albeit through appetite suppression rather than willpower and discipline. Perhaps, she reasoned, by slowing aging itself through the same calorie restriction effect, the drug would push back the diseases that aging can bring on. It worked.
Mice on semaglutide explored more, balanced longer on a rotating rod, ran farther on a treadmill and solved a maze faster—gains that held even after the researchers accounted for the animals just being leaner than their peers. Compared with the untreated animals, their tissues were less worn out and inflamed, and they died later.
Then Chen and her team set up a separate, five-month experiment in which a group of late-life mice got the drug while another group was simply fed 24 percent less—about the same amount of food as the treated mice had cut back on because of appetite suppression. Semaglutide treatment matched the diet on measures of muscle strength and coordination.
To see whether the drug works through the same biological mechanism as dieting, the team sequenced gene activity in the livers of treated mice and compared that to existing data on calorie restriction. The overlap was significant: both calorie restriction and the GLP-1 quieted down inflammation and fat processing, and both stepped up the genes for handling blood sugar and maintaining proteins. The results suggests semaglutide mimics calorie restriction but has an additional power: the GLP-1 mice had better memory scores, curiosity levels and blood sugar.
“In that sense, it’s more than just a calorie restriction,” Chen says. Why the drug apparently has this edge over dieting is unclear. “The short answer is: we don’t know yet,” she says.
The study doesn’t answer whether dieting or semaglutide extends the lifespan more. “Maybe calorie restriction increases the lifespan more?” wonders Nir Barzilai, a longevity researcher at the Albert Einstein College of Medicine who was not involved in the study. “The data is not there, and it bugs me.” It bugs Chen, too.
That experiment is currently ongoing, she says. “I don’t predict what the results might be. The results always surprise us.”