Researchers at UC Berkeley report that semaglutide improved muscle and cognitive function, reduced hallmarks of ageing and extended median lifespan by nearly 100 days in older female mice.
The GLP-1 drug semaglutide may slow aspects of biological ageing and extend lifespan, according to a new study of older, healthy mice funded by the National Institutes of Health (NIH).
Researchers at the University of California, Berkeley found that three months of treatment improved muscle and cognitive function in older female mice while reducing several biological markers associated with ageing. In a separate group followed until death, mice receiving semaglutide had a median lifespan almost 100 days longer than untreated animals.
The findings add to evidence that GLP-1 drugs, which have already been linked to a lower risk of several age-related diseases in animals, could affect the ageing process itself rather than simply treating individual conditions.
“Most chronic diseases are deeply rooted in the ageing 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 Dr Rafael de Cabo, a senior investigator at the NIH’s National Institute on Aging (NIA), and author of a commentary on the new study.
Similar effects to calorie restriction
The researchers, led by Dr Danica Chen, Professor of Metabolic Biology and Nutrition at UC Berkeley, gave semaglutide to 20-month-old female mice for three months to examine its effects at an advanced stage of life.
Compared with untreated mice, those given the drug performed better in measures of muscle and cognitive function. Gene expression analysis also indicated reductions in several hallmarks of natural ageing, including increased inflammation and diminished regenerative capacity.
The team then investigated whether these effects were simply the result of mice eating less because of semaglutide’s known effects on appetite.
For five months, one group of 20-month-old female mice received semaglutide while another was placed on a 24 percent calorie-restricted diet designed to match the feeding pattern of the treated animals.
The researchers found substantial similarities between the groups, with most physiological measurements remaining stable. However, the semaglutide-treated mice exceeded baseline levels in exploratory behaviour, spatial memory and blood-sugar regulation.
The two groups also showed differences in metabolic rate. It fell in the calorie-restricted mice but remained largely unchanged among those receiving semaglutide.
Potential route beyond calorie restriction
The differences suggest semaglutide could produce some of its effects through biological mechanisms that are separate from simply reducing food intake.
“These differences point to the possibility that GLP-1 drugs tap into a biological pathway independent of calorie restriction,” said Chen. ”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.”
The researchers stressed that the findings in mice cannot yet be assumed to apply to people. Further clinical research will be needed to establish whether GLP-1 drugs can extend or otherwise improve healthy lifespan in humans.
Future studies could also examine whether GLP-1 drugs provide benefits for healthy older people, potentially expanding their use beyond the treatment of existing metabolic and age-related conditions.
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