GLP-1 Weight-Loss Drugs Can Slow Aging and Extend Life Span, Mouse Study Suggests
Older female mice—equivalent in age to 60-year-old women—given daily injections of the active ingredient in Ozempic lived about 12 percent longer than animals that didn’t receive the drug
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GLP-1 medicines like semaglutide—marketed as Ozempic and Wegovy—have become cultural sensations over the past few years. They mimic a natural hormone that triggers feelings of fullness and helps regulate blood sugar. In addition to treating obesity and type 2 diabetes, the drugs have been greenlit in the United States for reducing the risk of cardiovascular events and kidney disease progression, as well as easing sleep apnea.
Now, new research hints that the blockbuster drugs might have yet another benefit: slowing aging. Giving semaglutide to elderly female mice extended their life spans while blunting several cellular hallmarks of getting old, according to a study published in the journal Nature on September 2.
Humanity has long hunted for a panacea that can turn back the clock on aging. In the past century, scientists have realized that restricting calorie intake can extend life span, but strict diets are notoriously difficult for people to sustain. Danica Chen, an aging biologist at the University of California, Berkeley, wondered if a certain pharmaceutical elixir could offer the anti-aging perks of a low-calorie diet without the constant pangs of hunger.
“Because the GLP-1 medicines reduce food intake, it’s sort of natural for us to ask if GLP-1 medicines actually function as calorie-restriction mimetics to slow aging and extend life span,” she tells Chemical and Engineering News’ Laurel Oldach.
To test this hypothesis, Chen and colleagues injected 20-month-old female mice—roughly equivalent to 60-year-old women—with semaglutide every day for the rest of their lives, while a control group received saline shots. The median life span of saline-treated mice was 742 days, while that of semaglutide-treated mice was 834 days, a 12 percent increase.
Need to know: Why only females?
The researchers didn’t include male mice because they are more aggressive, which could complicate the study’s findings.
Mice given the GLP-1 also exhibited remarkable physical and cognitive abilities. After just three months of treatment, the animals were noticeably more active, curious and sprightly than those not on the drug. They performed better at physical tasks: balancing longer on rotating rods, running farther on a treadmill and navigating a maze faster. Molecular analyses also showed the treated mice’s tissues had blunted hallmarks of aging, such as DNA damage and inflammation.
But how do the effects of semaglutide compare to those of calorie restriction? The team investigated by pitting GLP-1 mice, which had self-reduced their food intake by 24 percent, against animals whose diets were restricted by the same amount by the researchers.
Both regimes led to similar life spans and performances in some tests, such as those of endurance and motor coordination. However, the semaglutide-treated mice displayed enhancements in tests of memory and exploration. They also had better glucose tolerance.
The findings suggest that semaglutide’s potential longevity benefits come from “more than just calorie restriction,” Chen tells Scientific American’s Jacek Krywko. But what drives these effects of the GLP-1 remains unknown.
“This is a very rigorous animal study that showed a positive signal,” Michael Corley, an aging biologist at the University of California, San Diego, who wasn’t involved in this study, tells Nature’s Mariana Lenharo.
Still, more testing in mice is needed, especially because the study involved only female animals. “One intervention that works in one gender does not necessarily generalize to another gender,” Ho Ko, a neuroscientist at the Chinese University of Hong Kong, tells Nature.
A deeper clinical concern is the risk of muscle loss that often accompanies GLP-1 use, although it’s typically associated with weight loss in general no matter the tool. But that’s particularly concerning in older adults, who are already losing muscle mass due to natural processes of aging. Trying to extend life span with semaglutide may therefore accelerate frailty, Matt Mendoza, a neuroscientist at the University of Texas Medical Branch, tells C&EN.
“Skeletal muscle is your largest endocrine organ,” he says. Exercise is crucial to combat potential muscle loss.