Fig. 1

Experimental protocols. Aged mice were administered intraperitoneally with 4-Octyl itaconate (OI) or/and ML385 (an antagonist of Nrf2) 1 h after exploratory laparotomy under isoflurane anesthesia. Intestinal contents, blood, and brain tissue were collected for 16S rRNA gene sequencing, metabolomics, ELISA, and immunofluorescence analysis 24 h after surgery. Another cohort of aged mice underwent the open-field test (OFT) and new object recognition (NOR) test on postoperative days 5 and 6. Subsequently, 5-ethynyl-2′-deoxyuridine (EDU) was intraperitoneally injected into aged mice for 3 days, and brain tissue was collected for immunofluorescence analysis 9 days after surgery