GLP-1 drugs are best known for helping people manage type 2 diabetes and lose weight. New animal research raises a much bigger question: Could some of their effects reach beyond appetite and body weight?
In a study of older female mice, researchers found that the GLP-1 drug semaglutide extended lifespan and improved several measures of physical function, memory and blood sugar control. The treatment also produced many of the same changes seen with calorie restriction, which has long been known to extend lifespan in laboratory animals. In some areas, though, the drug appeared to do more than eating fewer calories alone. The findings do not show that GLP-1 drugs slow aging or extend life in people.
The study was published in Nature and led by researchers at the University of California, Berkeley. The Regents of the University of California have filed a patent application covering the use of GLP-1 receptor agonists for healthy aging, an important potential conflict to keep in mind when interpreting the findings.
Researchers began treating female mice at 20 months old, an age when declines associated with aging are already underway. One group received semaglutide daily for the rest of their lives, while another group received no active treatment.
The mice receiving the drug lived substantially longer. Their median lifespan was 834 days, compared with 742 days for untreated mice, a difference of 92 days.
In a separate group treated for three months, the drug was also associated with better performance on tests of movement, muscle function, endurance, memory and blood sugar control. Researchers also found improvements in several biological changes commonly seen with aging, including inflammation, cellular damage and declines in some types of stem cells.
But GLP-1 drugs also reduce appetite, and the treated mice ate about 24% less. That raised an obvious question: Were the benefits simply the result of eating fewer calories?
To find out, the researchers directly compared the drug with calorie restriction.
Another group of older mice received 24% fewer calories, closely matching the reduction in food intake seen in the drug-treated animals. Both approaches led to similar losses in body weight and body fat and helped preserve several aspects of physical function as the mice aged.
But the two approaches were not identical.
The calorie-restricted mice tended to eat their allotted food quickly and then go through a long fasting period. Mice given the GLP-1 drug ate more gradually throughout the day, consistent with its appetite-suppressing effects.
More importantly, the drug-treated mice appeared to do better on several measures. While calorie restriction generally helped maintain function, the GLP-1 treatment improved exploratory behavior, spatial memory and blood sugar control beyond where the mice had started.
Those differences suggest that at least some of the drug’s effects may not come simply from eating less.
Study author Danica Chen said the findings point toward the possibility that GLP-1 drugs influence biological pathways beyond calorie reduction alone. That could help researchers understand why these medications have shown benefits involving several different organs and health conditions.
But that possibility is still a long way from showing that GLP-1 drugs can slow aging in people.
This study involved only female mice. Researchers chose females in part to avoid injuries and other complications linked with aggression among male mice, but that also means the results cannot automatically be applied to males. The lifespan experiment included 39 untreated mice and 40 mice receiving the drug, while many of the other tests involved much smaller groups.
There is also a major difference between improving signs associated with aging in mice and extending healthy life in humans.
Researchers measured changes in inflammation, cellular function, physical performance and other features that tend to worsen with age. Those findings can help scientists understand what may be happening biologically, but they do not establish that the same effects would occur in people taking GLP-1 drugs.
Human studies have already found benefits from GLP-1 medications beyond weight loss in certain groups, including improvements in cardiovascular, kidney and liver outcomes. What remains unknown is whether those benefits reflect any broader effect on the aging process itself.
The authors say answering that question would require long-term clinical studies designed specifically to follow aging-related outcomes in older adults.
For now, the most interesting part of the study may not be whether GLP-1 drugs could become longevity treatments. It is the evidence that some of their effects in mice may go beyond simply helping them eat less.
That distinction could eventually help researchers better understand why this class of drugs appears to affect so many different areas of health.
The study was supported by grants from the National Institute on Aging and the National Institute of Food and Agriculture. The Regents of the University of California have filed a patent application on the use of GLP-1 receptor agonists for healthy aging.