GLP-1R activation late in life extends lifespan and mitigates aging in aged female mice

Late-life treatment of 20‑month‑old female mice with the GLP‑1R agonist semaglutide reduced food intake and significantly extended median lifespan, while improving locomotion, cognition, and glucose control. Semaglutide also alleviated multiple aging hallmarks—e.g., inflammation, cellular senescence, genomic instability, and mitochondrial dysfunction—and promoted neurogenesis. Transcriptomic analyses showed activation of nutrient-sensing pathways and sirtuins, aligning with calorie restriction cues. In a direct comparison, semaglutide mimicked many calorie restriction benefits and offered additional improvements in exploration, memory, and metabolic health, supporting GLP-1R activation as a calorie restriction mimetic with potential anti-aging effects in humans.