Late-life semaglutide therapy extends lifespan and reverses aging markers in female mice
Administering the GLP-1 receptor agonist semaglutide to 20-month-old female mice for three months improved physiological function, reduced multiple hallmarks of aging, and lengthened median lifespan.
Researchers gave 20-month-old female C57BL/6 mice daily injections of semaglutide, a GLP-1R agonist, for three months, observing a 24% drop in food consumption and selective loss of fat mass. Functional testing showed heightened exploratory activity, superior motor coordination, increased endurance, and enhanced spatial memory, alongside more efficient glucose clearance and insulin signaling. At the cellular level, semaglutide lowered the number of aged hematopoietic stem cells, boosted hippocampal neurogenesis, dampened inflammatory cytokine expression, and decreased markers of senescence, DNA damage, and mitochondrial stress.
Transcriptomic profiling indicated down-regulation of lipid metabolism and inflammation and up-regulation of adaptive immunity, insulin response, and proteostasis, paralleling patterns seen with calorie restriction. Lifespan tracking demonstrated a median extension from 742 to 834 days, with delayed death across several non-tumor categories. The authors conclude that late-life GLP-1R activation acts as a calorie-restriction mimetic and may counteract age-related decline beyond mere appetite suppression.
Why it matters
The findings suggest a widely used diabetes drug could also delay aging and extend healthy lifespan.
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