A study supported by the National Institutes of Health (NIH) indicates that semaglutide, the active pharmaceutical ingredient in weight-loss and diabetes medications such as Ozempic and Wegovy, may extend lifespan and mitigate several hallmarks of aging in older mice. The findings, published in the journal Nature, suggest the drug could influence biological aging processes beyond its known effects on appetite suppression and blood sugar regulation.
Researchers from the University of California, Berkeley, led by Dr. Danica Chen, administered semaglutide to female mice that were 20 months old—equivalent to late middle age or older in human terms—for a period of three months. The treated animals exhibited significant improvements in muscle function, cognitive performance, and spatial memory compared to a control group that received no treatment.
Genetic analysis of the mice revealed favorable changes in biological markers associated with aging, including reduced inflammation and enhanced tissue repair and regeneration capabilities. In a separate cohort where the drug was administered until natural death, the median lifespan of semaglutide-treated mice was nearly 100 days longer than that of untreated counterparts.
To determine whether these anti-aging benefits were solely a result of reduced food intake, the researchers conducted a direct comparison with calorie restriction. For five months, one group of mice received semaglutide while another was placed on a diet restricting calories by 24%, matched to the intake levels of the drug-treated group.
While both interventions shared some physiological similarities, semaglutide demonstrated distinct advantages. Mice on the drug showed greater improvements in exploratory behavior and blood sugar maintenance. Furthermore, their metabolic rates remained stable, whereas the calorie-restricted mice experienced a slowdown in metabolism.
These differences led the authors to propose that GLP-1 drugs like semaglutide may activate biological pathways related to longevity that are separate from those triggered by eating less. “These differences point to the possibility that GLP-1 drugs tap into a biological pathway independent of calorie restriction,” Chen stated, noting that uncovering this mechanism is a key direction for future longevity research.
Rafael de Cabo, Ph.D., a senior investigator at the NIH’s National Institute on Aging who authored a commentary on the study, highlighted the broader implications. “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,” he said.
Despite the promising results in animals, the researchers cautioned that the study does not prove that Ozempic or Wegovy can extend human lifespan. Clinical trials are necessary to determine if these effects translate to people. Previous analyses, such as a post-hoc review of the SLIM LIVER trial, have begun exploring these questions, but more robust human data is needed.
Chen suggested that future clinical studies could investigate whether GLP-1 treatments offer similar benefits for healthy older adults without obesity or diabetes, which could significantly broaden the potential applications of these medications. The research was funded by NIH grants R01AG063404, R01AG063389, and R01AG082105.
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