Lycium barbarum glycopeptide ameliorates aging phenotypes and enhances cardiac metabolism by activating the PINK1/Parkin-mediated mitophagy pathway in D-galactose-induced mice

• Published in: Experimental gerontology 2025-02, Vol.200, p.112686, Article 112686
• Main Authors: Peng, Tianchan, Xiang, Jian, Tian, Yun, Tang, Xiaogen, Wang, Lina, Gao, Lijuan, Luo, Oscar Junhong, Huang, Li'an, Chen, Guobing
• Format: Article
• Language: English
• Subjects: Aging; Cardiac metabolism; D-galactose; Lycium barbarum glycopeptide; Mitophagy
• ISSN: 0531-5565; 1873-6815; 1873-6815
• DOI: 10.1016/j.exger.2025.112686

Aging is a complex biological process that disrupts tissue structure and impairs physiological function, which contributes to the development of age-related diseases such as cardiovascular disorders. However, effective treatment strategies are lacking. To investigate the geroprotective effects of Lycium barbarum glycopeptide (LbGp) and its potential mechanisms in a D-galactose-induced accelerated aging mouse model. Mice were subcutaneously injected with D-galactose (500 mg/kg/day) for 12 weeks to induce aging, while LbGp was orally administered (100 mg/kg/day) throughout the study. The geroprotective effects of LbGp were assessed by behavioral tests, cardiac echocardiography, pathohistological and transcriptomic analyses. Transmission electron microscopy was used to observe the ultrastructure of mitochondria. Mitochondrial stress assays and JC-1 fluorescent probe were conducted to evaluate mitochondrial function. Flow cytometer and western blot were performed to assess mitophagy flux. LbGp treatment improved the aging phenotypes of D-galactose-induced mice, with a pronounced enhancement in cardiac function compared to neurocognitive and skeletal muscle functions. Transcriptome analysis indicated that LbGp ameliorated energy metabolism in the heart. Mitochondrial assays revealed LbGp improved mitochondrial function and preserved structural integrity of the mitochondrial inner membrane. LbGp attenuated mitochondrial fission and restored impaired PINK1/Parkin-mediated mitophagy pathway caused by D-galactose in cardiomyocytes. LbGp can ameliorate aging phenotypes and enhance cardiac metabolism by activating the PINK1/Parkin-mediated mitophagy pathway in D-galactose-induced mice. These findings underscore its potential as a therapeutic agent for aging and aging-related cardiovascular diseases.