Zhang Yue, Wu Wenfang, Huang Caihua, Lin Donghai
Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.
Research and Communication Center of Exercise and Health, Xiamen University of Technology, Xiamen 361021, China.
J Proteome Res. 2025 Feb 7;24(2):834-849. doi: 10.1021/acs.jproteome.4c00939. Epub 2025 Jan 8.
Skeletal muscle aging poses a major threat to the health and quality of life of elderly individuals. Fisetin, a natural polyphenolic compound, exhibits various biological activities; however, its role in preventing skeletal muscle cell aging is still unclear. This study aimed to elucidate the effects of fisetin on skeletal muscle aging using a d-galactose-induced C2C12 myoblast senescence model. Fisetin treatment effectively ameliorated d-galactose-induced aging damage and restored cellular functionality by improving cell viability, reducing the accumulation of the senescence marker enzyme SA-β-gal, and decreasing the expression of key aging marker proteins, p16 and p53. NMR-based metabolomics and RNA-seq transcriptomics analyses revealed that fisetin regulates several critical metabolic pathways, including glutathione metabolism, glycine, serine and threonine metabolism, as well as taurine and hypotaurine metabolism. This regulation led to the restoration of amino acid metabolism, stabilization of cellular energy homeostasis, and the preservation of membrane integrity. In addition, fisetin inhibited calcium signaling and JAK-STAT pathways, reduced cellular stress responses and reversed senescence-induced cell cycle arrest. Together, these findings highlight the potential of fisetin as a therapeutic agent to combat skeletal muscle aging and restore cellular homeostasis, offering a promising avenue for the development of antiaging treatments for skeletal muscle degeneration.
骨骼肌衰老对老年人的健康和生活质量构成重大威胁。漆黄素是一种天然多酚化合物，具有多种生物活性；然而，其在预防骨骼肌细胞衰老中的作用仍不清楚。本研究旨在利用d-半乳糖诱导的C2C12成肌细胞衰老模型阐明漆黄素对骨骼肌衰老的影响。漆黄素处理可有效改善d-半乳糖诱导的衰老损伤，并通过提高细胞活力、减少衰老标记酶SA-β-半乳糖的积累以及降低关键衰老标记蛋白p16和p53的表达来恢复细胞功能。基于核磁共振的代谢组学和RNA测序转录组学分析表明，漆黄素调节多种关键代谢途径，包括谷胱甘肽代谢、甘氨酸、丝氨酸和苏氨酸代谢以及牛磺酸和亚牛磺酸代谢。这种调节导致氨基酸代谢的恢复、细胞能量稳态的稳定以及膜完整性的维持。此外，漆黄素抑制钙信号和JAK-STAT途径，减少细胞应激反应并逆转衰老诱导的细胞周期停滞。总之，这些发现突出了漆黄素作为一种治疗剂对抗骨骼肌衰老和恢复细胞稳态的潜力，为骨骼肌退化的抗衰老治疗开发提供了一条有前景的途径。
