Semaglutide, the active ingredient in popular GLP-1 drugs such as Ozempic and Wegovy, may do more than suppress appetite and improve blood sugar. A National Institutes of Health (NIH) funded study found that the drug reduced several harmful effects of aging and extended lifespan in older, healthy mice.
Researchers at the University of California, Berkeley compared semaglutide directly with calorie restriction, one of the best-known interventions for extending lifespan in laboratory animals. The drug reproduced many of the anti-aging effects of eating less, but in several important areas, it appeared to go even further.
The findings raise an intriguing possibility: GLP-1 drugs may influence the aging process itself. Earlier animal studies have shown that these drugs can delay the onset of multiple age-related diseases. If semaglutide acts on biological mechanisms that drive aging, that could help explain why GLP-1 treatments have shown benefits across such a wide range of health conditions.
“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.
Testing Semaglutide Late in Life
To see what semaglutide could do when aging was already well underway, a research team led by Danica Chen, Ph.D., gave the drug to 20-month-old female mice for three months.
Compared with untreated mice, the animals receiving semaglutide showed better muscle and cognitive function. Gene activity also revealed improvements in several biological features associated with aging, including reduced inflammation and less decline in the body’s ability to repair and regenerate tissue.
The lifespan results were especially striking. In a separate group treated with semaglutide until death, median lifespan was nearly 100 days longer than in untreated mice.
Was Eating Less the Real Reason?
Because semaglutide reduces appetite, the researchers wanted to know whether the apparent anti-aging effects simply came from consuming fewer calories.
To test that idea, they directly compared semaglutide with calorie restriction. For five months, one group of 20-month-old female mice received semaglutide, while another was placed on a 24% calorie-restricted diet designed to match how much the treated mice were eating.
The two approaches produced many similar effects, and most physiological measurements remained stable. But semaglutide stood out in several areas.
Mice receiving the drug improved beyond their starting levels in exploratory behavior, spatial memory, and blood-sugar maintenance. Their metabolic rate also remained largely unchanged, while metabolism slowed in the calorie-restricted animals.
Those differences suggest that semaglutide may be doing more than simply recreating the effects of eating less.
“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.
Could GLP-1 Drugs Affect Human Aging?
The findings could open new directions in longevity research, but they do not show that Ozempic, Wegovy, or other GLP-1 drugs can extend human lifespan.
Additional clinical research will be needed to determine whether the effects seen in mice translate to people. One example is the recent post-hoc analysis of the SLIM LIVER trial, but further studies will be necessary to establish whether GLP-1 drugs can meaningfully influence human aging or longevity.
Chen said future clinical studies may also investigate these drugs in healthy older adults. If researchers eventually find similar benefits in people without obesity or diabetes, the potential uses of GLP-1 treatments could broaden considerably.
NIH supported this research through NIA grants R01AG063404, R01AG063389, and R01AG082105.
