Researchers say that starting an aging mouse on semaglutide can extend its lifespan and delay certain well-known hallmarks of aging (Nature 2026, DOI: 10.1038/s41586-026-10940-7). If the results are borne out in human trials, it’s yet another lucrative possible indication for the GLP-1 agonists, which are widely used as weight-loss and antidiabetic medicines and also have been shown to reduce heart attacks and all-cause mortality in cohorts with those ailments.
Researchers have known for decades that caloric restriction can delay aging in animals. It can work in humans, too—but crash diets are difficult to maintain. So longevity researchers have been on the hunt for caloric-restriction mimetics that people can live with.
“Because the GLP-1 medicines reduce food intake, it’s sort of natural for us to ask if GLP-1 medicines actually function as calorie-restriction mimetics to slow aging and extend lifespan,” says Danica Chen, a metabolic biologist at the University of California, Berkeley, who led the study.
Starting with female mice that were 20 months old—the mouse equivalent of a 60-year-old woman, Chen says—researchers in her lab gave one cohort a daily semaglutide injection and the other a saline shot, for as long as they lived. The saline-treated mice survived for a median 4.7 months after the study began, compared with 7.8 months for the semaglutide cohort.
The scientists also tested other cohorts of aging mice to learn how semaglutide affected their biochemistry and behavior. After as little as 3 months, the treated mice were more sprightly and curious than their peers, with better glucose control and exercise endurance. Stem cells in their bone marrow and in parts of their brains showed better regenerative capacity.
The researchers measured a number of biochemical hallmarks of aging, including an increase in inflammation and NAD+. “Stem cell decline, DNA damage, loss of protein homeostasis, mitochondrial function . . . these are all well established, and they’re all important,” Chen says. Across the board, the effects of aging were blunted.
When the researchers compared calorically restricted mice with semaglutide-treated mice, Chen says, she was surprised to observe that the drug appeared to improve cognition and glucose control above the caloric-restriction baseline. “To me, it’s not just slowing aging but reversing aging-associated decline,” she says.
“Semaglutide is probably the best caloric-restriction mimetic I have seen” based on the data available so far, says Tim Rhoads, who studies aging at the University of Wisconsin–Madison and was not involved with the study.
One thing that surprises Rhoads is that semaglutide-treated mice tended to eat on a roughly normal schedule. In contrast, mice on a restricted diet show signs of hunger: they begin to forage before feeding time and gobble their daily ration as soon as it becomes available.
Researchers have some evidence that the mild stress of a long fasting period before the next food pellets drop contributes to metabolic well-being, fueling the intermittent-fasting fad diet. But the mice on semaglutide seemed to reap those same metabolic benefits without the stress.
The caveats, Rhoads says, are that researchers will need to test semaglutide in male mice, too, and may need to be concerned about the loss of muscle mass that semaglutide can cause.
Because medical regulators don’t recognize aging as a disease, only a few small studies so far are specifically investigating GLP-1 drugs for longevity.
Matt Mendoza, an associate director at the Moody Brain Health Institute at the University of Texas Medical Branch (UTMB), runs one of those trials with colleagues. He shares Rhoads’s concern about potentially accelerating frailty through the loss of muscle mass. “Skeletal muscle is your largest endocrine organ,” Mendoza says; participants in the UTMB study are also advised to exercise to retain muscle.
Another important question for future research, Mendoza says, is whether dual agonists that target both GLP-1 and GIP might show greater effects, as they have in other diseases; that’s part of why his team chose to test the dual agonist tirzepatide.
