The medication provided benefits beyond those achieved through calorie restriction alone.
A medication widely used for diabetes and weight loss may also be affecting some of the biology of aging. Semaglutide, the active ingredient in Ozempic, Wegovy, and Rybelsus, is a GLP-1 drug that helps regulate blood sugar and reduce appetite. It improved muscle and cognitive function and reduced several age-related changes in older, healthy female mice. In a separate experiment, mice treated with the drug until the end of life had a median lifespan nearly 100 days longer than untreated animals.
But semaglutide also causes animals to eat less, raising an important question. Were the mice benefiting from the drug itself, or simply from consuming fewer calories?
To find out, researchers at the University of California, Berkeley compared semaglutide directly with calorie restriction. The two approaches produced many similar effects, but several benefits in the semaglutide-treated mice went beyond what researchers observed from eating less alone.
That distinction matters because calorie restriction has long been associated with longer life and slower aging in laboratory animals. If semaglutide produces additional effects through a different biological pathway, it could help researchers understand why GLP-1 drugs have shown benefits across several age-related diseases in animal studies.
“Most chronic diseases are deeply rooted in the aging process. If GLP-1 agonists do indeed slow it down, then a wide range of clinical benefits is exactly what you’d expect to see,” said Rafael de Cabo, Ph.D., a senior investigator at the NIH’s National Institute on Aging (NIA), and author of a commentary on the new study.
Older mice showed broader benefits
The NIH-funded study, led by Danica Chen, Ph.D., examined what happened when semaglutide was given late in life, when the effects of aging were already more pronounced. The researchers treated 20-month-old female mice with the drug for three months.
Compared with untreated mice, the semaglutide group showed improved muscle and cognitive function. The researchers also analyzed gene activity and found reductions in several hallmarks of natural aging, including increased inflammation and reduced regenerative capacity.
Another group of mice received semaglutide until the end of life. Their median lifespan was nearly 100 days longer than that of untreated mice.
Eating less did not explain everything
Those findings alone could not reveal whether semaglutide was directly influencing aging, because the drug also reduces food intake. To separate the effects of the medication from those of eating less, the researchers conducted a second comparison.
One group of 20-month-old female mice received semaglutide for five months. Another group ate a diet containing 24% fewer calories, designed to match the feeding pattern of the animals receiving the drug.
Many physiological measurements remained stable in both groups, showing that semaglutide and calorie restriction produced several similar effects. But the two approaches were not identical.
Mice treated with semaglutide improved beyond their starting levels in exploratory behavior, spatial memory, and blood sugar maintenance. Their metabolic rate also remained largely unchanged, while it declined in mice on the calorie-restricted diet.
Those differences suggest that reduced food intake may not fully account for semaglutide’s effects.
“These differences point to the possibility that GLP-1 drugs tap into a biological pathway independent of calorie restriction. Uncovering this potential route and the benefits that may specifically stem from it is an important direction for future research into the development of longevity-enhancing interventions,” said Chen, corresponding author of the study and professor of metabolic biology and nutrition at UC Berkeley.
Human longevity remains unproven
Previous animal studies have found that GLP-1 drugs can delay the onset of several diseases associated with aging. This research asked a broader question by studying otherwise healthy older mice: whether semaglutide might also influence the physiological aging process itself.
The results do not show that semaglutide slows aging or extends lifespan in people. The experiments involved older female mice, and effects observed in laboratory animals do not necessarily translate to humans.
Clinical studies will be needed to determine whether similar effects occur in people. The researchers pointed to work such as a recent post-hoc analysis of the SLIM LIVER trial as part of the broader effort to understand whether GLP-1 drugs could influence longevity-related outcomes in humans.
Chen also said future studies could examine GLP-1 drugs in healthy older adults, which would expand research beyond people taking the medications for conditions such as obesity or type 2 diabetes.
For now, the findings suggest that semaglutide can reproduce some of the effects associated with calorie restriction in older mice while also producing benefits that eating less alone did not fully explain. Understanding what drives those differences could reveal whether GLP-1 drugs are acting on biological pathways that play a broader role in aging.
Reference: “Late-life semaglutide treatment slows ageing and extends lifespan in female mice” by Yufan Feng, Marine Barthez, Yifei Wang, Yibing Chen, Huixian Qiu, Chih-Ling Wang, Kartoosh Heydari, Melaine Delcroix, Lene Juel Rasmussen, Vilhelm A. Bohr and Danica Chen, 2 September 2026, Nature.
DOI: 10.1038/s41586-026-10940-7
NIH supported this research through NIA grants R01AG063404, R01AG063389, and R01AG082105.
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