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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2025-06-01
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| Online Access: | https://doi.org/10.1038/s41598-025-02707-3 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Ming Ann Sim |
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| description | 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. |
| format | Article |
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| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-06-01 |
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| series | Scientific Reports |
| spelling | doaj-art-8fd9717daabb42d9be6a907fad6594712025-08-20T03:26:44ZengNature PortfolioScientific Reports2045-23222025-06-011511910.1038/s41598-025-02707-3Effect of preoperative rapamycin supplementation on perioperative clinical frailty and cognitive performance in a murine model undergoing anesthesia and surgeryMing Ann Sim0Jorming Goh1Jasinda Lee2Jian Hua Tay3Francis Chee Kuan Tan4Chunmei Li5Esther S. P. Wong6Will N. H. Loh7Sophia T. H. Chew8Andrea B. Maier9Brian K. Kennedy10Lian Kah Ti11Centre for Healthy Longevity, Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of SingaporeCentre for Healthy Longevity, Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of SingaporeCentre for Healthy Longevity, Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of SingaporeDepartment of Medicine, Yong Loo Lin School of Medicine, National University of SingaporeYong Loo Lin School of Medicine, National University of SingaporeYong Loo Lin School of Medicine, National University of SingaporeCentre for Healthy Longevity, Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of SingaporeDepartment of Anesthesia, National University Health SystemYong Loo Lin School of Medicine, National University of SingaporeDepartment of Medicine, Yong Loo Lin School of Medicine, National University of SingaporeCentre for Healthy Longevity, Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of SingaporeCentre for Healthy Longevity, Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of SingaporeAbstract 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.https://doi.org/10.1038/s41598-025-02707-3AgingRapamycinPerioperativeCognitionFrailtyAnesthesia |
| spellingShingle | 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 Effect of preoperative rapamycin supplementation on perioperative clinical frailty and cognitive performance in a murine model undergoing anesthesia and surgery Scientific Reports Aging Rapamycin Perioperative Cognition Frailty Anesthesia |
| title | Effect of preoperative rapamycin supplementation on perioperative clinical frailty and cognitive performance in a murine model undergoing anesthesia and surgery |
| title_full | Effect of preoperative rapamycin supplementation on perioperative clinical frailty and cognitive performance in a murine model undergoing anesthesia and surgery |
| title_fullStr | Effect of preoperative rapamycin supplementation on perioperative clinical frailty and cognitive performance in a murine model undergoing anesthesia and surgery |
| title_full_unstemmed | Effect of preoperative rapamycin supplementation on perioperative clinical frailty and cognitive performance in a murine model undergoing anesthesia and surgery |
| title_short | Effect of preoperative rapamycin supplementation on perioperative clinical frailty and cognitive performance in a murine model undergoing anesthesia and surgery |
| title_sort | effect of preoperative rapamycin supplementation on perioperative clinical frailty and cognitive performance in a murine model undergoing anesthesia and surgery |
| topic | Aging Rapamycin Perioperative Cognition Frailty Anesthesia |
| url | https://doi.org/10.1038/s41598-025-02707-3 |
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