Semaglutide, the weight loss drug marketed as Ozempic and Wegovy, has extended the lifespan of mice that started receiving it at an advanced age by 12%, according to research led by the University of California, Berkeley, published today in the journal Nature. The increase in longevity has been accompanied by improvements in aging indicators related to cognitive functions, immunity, metabolism, activity level, and blood cell regeneration, among others. Future studies will need to clarify whether these benefits extend to people taking semaglutide or similar drugs, as the researchers suspect.
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The results indicate that these drugs have effects equivalent to caloric restriction, which delays aging and extends life in animals but is unpleasant for people. Caloric restriction involves reducing calorie intake without reaching malnutrition.
The research was based on administering semaglutide to mice starting at twenty months of age, comparable to about 70 years in humans. “We administered doses equivalent to those prescribed to people,” Danica Chen, a longevity medicine specialist at Berkeley and director of the study, told La Vanguardia.
Semaglutide reproduces positive effects of caloric restriction without causing an unpleasant feeling of hunger
The animals treated with semaglutide lived a median of 834 days, compared to 742 days for the control group that did not receive the drug, representing a 12% increase in average survival.
Maximum survival also increased, with longevity of more than 900 days for nearly 20% of the mice treated with semaglutide, a figure not reached by any of the mice in the control group.
Equally important, the lifespan extension was accompanied by improved health at advanced ages. The animals that received the drug ran longer and farther in endurance tests. They showed better muscle function in fall tests. They exhibited more exploratory behavior when discovering new environments. Overall, they consumed 24% less food than untreated animals. But the observed benefits go beyond weight loss.
Treatment with semaglutide slowed the loss of neural stem cells in the hippocampus, a key brain region for learning, memory, and spatial orientation that degrades with age. It reduced inflammation and cellular senescence. It improved the regenerative capacity of blood stem cells in the bone marrow. It enhanced genome stability, response to oxidative stress, lipid metabolism, and insulin sensitivity, among other benefits.
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In one of the experiments, the researchers compared mice treated with semaglutide with others subjected to caloric restriction. The physiological effects were similar in both cases, but the effects on behavior were different. Both groups consumed the same amount of food. But while the animals treated with semaglutide ate throughout the day, the caloric restriction group was more restless before eating and ate quickly as soon as they could. It is a “hunger-driven behavior,” the researchers write in Nature.
The experiments were conducted only with females to minimize confounding effects of male aggression. “We believe the data can be extrapolated to male mice,” explains Danica Chen, although “we still have to do the experiment” to confirm it.
Semaglutide acts by mimicking the action of the GLP-1 hormone, which is produced in the digestive system after eating. Therefore, it is expected that the observed benefits will extend to other drugs that act similarly, such as tirzepatide (marketed as Mounjaro).
These drugs were initially developed for type 2 diabetes and later shown to be effective for obesity. More recently, they have been found to improve the treatment of liver, heart, or kidney diseases, as well as sleep apnea, in people with overweight or diabetes. Their usefulness for treating alcoholism and other addictions is also being studied.
The new research expands their potential benefits to healthy aging in people without prior pathologies. “There is a need to identify caloric restriction mimetics that retain its health and longevity benefits and are suitable for human applications,” the authors write in Nature. But they warn that “long-term clinical studies will be necessary” to demonstrate whether these drugs have an anti-aging effect in people.
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