▲ Wegovy, a GLP-1 receptor agonist diabetes and obesity treatment
Glucagon-like peptide-1 receptor agonists (GLP-1RAs, semaglutide), used to treat obesity and type 2 diabetes, have been shown in a research study to slow age-related functional decline and extend the lifespan of mice.
A research team led by Professor Danica Chen at the University of California, Berkeley (UC Berkeley) announced in the scientific journal Nature that administering semaglutide to elderly female mice improved their physiological and cognitive functions, alleviated various hallmarks of aging, and extended their lifespan by 92 days compared to a control group.
The research team noted that while this effect appears similar to calorie restriction—which has been linked to health and lifespan extension in multiple studies—GLP-1 drugs also showed effects that cannot be explained solely by a reduction in caloric intake. They stated that long-term clinical studies are needed to determine whether similar impacts occur on human aging and lifespan.
Calcalorie restriction, which reduces calorie intake within a range that does not cause malnutrition, is known to slow aging and extend lifespan in various species, alongside improvements in physiological function and the mitigation of metabolic and neurodegenerative diseases.
Semaglutide, the active ingredient in Ozempic and Wegovy, reduces food intake and is widely used as an effective treatment for type 2 diabetes and obesity.
The research team pointed out that while GLP-1 class drugs not only lower blood sugar and reduce body weight but also exert positive effects on various bodily functions, little is known about why these diverse effects occur.
The research team divided 20-month-old female mice into a semaglutide-treated group, a control group, and a calorie-restricted group to investigate the effects of semaglutide on the lifespan and physical function of aging mice, comparing the results with the calorie-restricted group.
As a result, the semaglutide-treated group showed improvements in physiological and cognitive functions and a mitigation of various hallmarks of aging. Mice receiving continuous semaglutide treatment achieved a median lifespan of 834 days, which was 92 days (about 12.4%) longer than the control group (742 days).
Additionally, to determine whether the effects of semaglutide were simply the result of reduced food intake, researchers compared the treatment group with a calorie-restricted group whose food intake was reduced by 24%. While reductions in body weight and body fat were similar, the fasting-induced behavioral and metabolic changes observed in the calorie-restricted group were not present in the semaglutide-treated group.
In terms of function, both groups showed similar effects such as the alleviation of age-related declines in motor and muscle function; however, the semaglutide-treated group demonstrated improvements exceeding baseline functional levels at the start of treatment in exploratory behavior, spatial memory, and blood glucose control.
Furthermore, the semaglutide-treated group exhibited an attenuation of biological changes associated with aging, including reduced bone marrow hematopoietic stem cell aging, enhanced regenerative capacity per cell, increased neural stem cell activity and neurogenesis in the dentate gyrus of the brain's hippocampus, and decreased inflammation and cellular senescence.
Liver gene expression analysis revealed that semaglutide induced changes that lowered the activity of genes related to inflammation and lipid metabolism while enhancing adaptive immune responses, insulin responses, and protein homeostasis.
The research team explained that various effects not fully explained by reduced food intake alone were identified in the semaglutide-treated group, suggesting that semaglutide may influence aging in ways that go beyond mere caloric reduction.
They added that while calorie restriction has been studied as a method to slow aging and extend lifespan by reducing caloric intake, it is difficult to maintain over the long term, and this study suggests that semaglutide has the potential to be utilized as a drug that mimics the benefits of calorie restriction.
"Uncovering the biological pathways through which GLP-1 drugs operate and the specific benefits derived from those pathways is an important direction for research on lifespan-extending interventions," Dr. Chen said, adding, "These results can provide important guidance for future research."
"In future clinical studies, we will also be able to examine the benefits of semaglutide in healthy older adults," she noted, adding, "Through this, the scope of applications for GLP-1 drugs could be significantly expanded."
(Photo: AP, Yonhap News)
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