Effect of preoperative rapamycin supplementation on perioperative clinical frailty and cognitive performance in a murine model undergoing anesthesia and surgery

Abstract The geroprotective effects of rapamycin in mitigating frailty and cognitive complications in the perioperative period remains unknown. Of 39 C57BL/6 mice tested, 19 were young (16 weeks), and 20 were old (80 weeks). The interventional group (10 old, 10 young) received daily oral rapamycin f...

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Main Authors: Ming Ann Sim, Jorming Goh, Jasinda Lee, Jian Hua Tay, Francis Chee Kuan Tan, Chunmei Li, Esther S. P. Wong, Will N. H. Loh, Sophia T. H. Chew, Andrea B. Maier, Brian K. Kennedy, Lian Kah Ti
Format: Article
Language:English
Published: Nature Portfolio 2025-06-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-02707-3
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Summary:Abstract The geroprotective effects of rapamycin in mitigating frailty and cognitive complications in the perioperative period remains unknown. Of 39 C57BL/6 mice tested, 19 were young (16 weeks), and 20 were old (80 weeks). The interventional group (10 old, 10 young) received daily oral rapamycin for 8 weeks pre-op compared to controls (10 old, 9 young). Sham laparotomy was performed at week 9. Perioperative frailty was assessed using a murine clinical frailty scale, preoperatively and at 1, 4 and 8 weeks postoperatively. Spatial memory was assessed using the Barnes maze preoperatively, and at weeks 1 and 4 post-op. Rapamycin treatment is associated with significantly less decline in postoperative clinical frailty(p < 0.05). Subgroup analysis revealed similar findings for old and young mice. The rapamycin group demonstrated improved cognitive performance at 1-week postoperatively (β 40.18, 95%C.I. 8.70–71.67, p = 0.012), but only in older mice (β 54.51, 95%C.I. 6.77–102.25, p = 0.025). In a pre-clinical animal model of anesthesia and surgery, rapamycin supplementation protected against surgery-induced frailty and short-term postoperative cognitive dysfunction.
ISSN:2045-2322