Late-life treatment with the GLP-1 receptor agonist semaglutide extended lifespan, preserved physical function, and improved memory in female mice. Digest
Calorie restriction does more than reduce body fat; it also changes how cells maintain and repair themselves. Researchers investigated whether semaglutide, a GLP-1 receptor agonist widely used for weight loss, could reproduce some of those effects when given late in life.
The experiments began in female mice at 20 months of age. One randomized comparison followed 40 mice receiving daily semaglutide and 39 receiving inactive saline injections until their death. Separate mice underwent three months of treatment before tests of memory, physical abilities and glucose control, alongside cellular studies. To examine how reduced food intake could explain test results, another experiment assigned 10 mice per group to semaglutide, saline, or a 24% calorie-restricted diet for five months. That restriction matched the average drop in food intake with semaglutide.
- Median total lifespan reached 834 days with semaglutide versus 742 days with saline, a difference of 92 days or 12%.
- In the separate three-month experiment, semaglutide-treated mice had better spatial memory, coordination, muscle performance, endurance, and glucose control than saline-treated mice. The coordination and muscle-performance advantages remained after accounting for body weight.
- In the additional five-month experiment, both semaglutide and the calorie-restricted diet preserved movement, coordination, muscle performance, and endurance over the first four months, while saline-treated mice declined. Semaglutide and calorie restriction produced comparable reductions in weight and body fat.
- In that same experiment, semaglutide produced more favorable changes in spatial memory, exploratory behavior, and blood glucose control than the calorie-restricted diet.
One possible link between eating less and aging better is the work cells do to maintain their proteins. Proteins need the right shape to function, and cells use quality-control systems to help fold them or break them down. Semaglutide shifted gene activity toward this maintenance work and away from inflammation, changes that overlapped with those associated with calorie restriction. It also reduced signs of protein-folding stress in stem cells that produce blood cells and neurons. Semaglutide may help preserve tissue function as animals age by supporting this cellular upkeep, rather than simply reducing body weight.
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Comparable reductions in body weight achieved with semaglutide or reduced access to food did not produce the same health benefits. Because GLP-1 receptors are found throughout the body, semaglutide may influence how tissues age in ways that go beyond reducing food intake.