Caloric restriction increases the resistance of aged heart to myocardial ischemia/reperfusion injury via modulating AMPK-SIRT 1 -PGC 1a energy metabolism pathway

• Published in: Scientific reports 2023-02, Vol.13 (1), p.2045
• Main Authors: Guo, Zhijia, Wang, Meng, Ying, Xiaodong, Yuan, Jiyu, Wang, Chenggang, Zhang, Wenjie, Tian, Shouyuan, Yan, Xiaoyan
• Format: Article
• Language: English
• Subjects: AMP-Activated Protein Kinases - metabolism; Animals; Caloric Restriction; Energy Metabolism; Mice; Mice, Inbred C57BL; Myocardial Reperfusion Injury; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
• ISSN: 2045-2322
• DOI: 10.1038/s41598-023-27611-6

A large number of data suggest that caloric restriction (CR) has a protective effect on myocardial ischemia/reperfusion injury (I/R) in the elderly. However, the mechanism is still unclear. In this study, we created the I/R model in vivo by ligating the mice left coronary artery for 45 min followed by reperfusion. C57BL/6J wild-type mice were randomly divided into a young group fed ad libitum (y-AL), aged fed ad libitum (a-AL) and aged calorie restriction group (a-CR, 70% diet restriction), and fed for 6 weeks. The area of myocardial infarction was measured by Evan's blue-TTC staining, plasma cholesterol content quantified by ELISA, fatty acids and glucose measured by Langendorff working system, as well as protein expression of AMPK/SIRT /PGC signaling pathway related factors in myocardial tissue detected by immunoblotting. Our results showed that CR significantly reduced infarct size in elderly mice after I/R injury, promoted glycolysis regardless of I/R injury, and restored myocardial glucose uptake in elderly mice. Compared with a-AL group, CR significantly promoted the expression of p-AMPK, SIRT , p-PGC , and SOD , but decreased PPARγ expression in aged mice. In conclusion, our results suggest that CR protects elderly mice from I/R injury by altering myocardial substrate energy metabolism via the AMPK/SIRT /PGC pathway.