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

IF 3.9 Experimental gerontology Pub Date : 2025-01-18 DOI:10.1016/j.exger.2025.112686

Tianchan Peng, Jian Xiang, Yun Tian, Xiaogen Tang, Lina Wang, Lijuan Gao, Oscar Junhong Luo, Li'an Huang, Guobing Chen

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Abstract

Background: 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.

Objective: To investigate the geroprotective effects of Lycium barbarum glycopeptide (LbGp) and its potential mechanisms in a D-galactose-induced accelerated aging mouse model.

Methods: 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.

Results: 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.

Conclusion: 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.

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枸杞糖肽通过激活d -半乳糖诱导小鼠的PINK1/帕金森介导的线粒体自噬途径，改善衰老表型并增强心脏代谢。

背景：衰老是一个复杂的生物过程，它会破坏组织结构，损害生理功能，从而导致心血管疾病等与年龄相关的疾病的发生。然而，缺乏有效的治疗策略。目的：探讨枸杞糖肽（LbGp）在d -半乳糖诱导的加速衰老小鼠模型中的保护作用及其可能机制。方法：小鼠皮下注射d -半乳糖（500 mg/kg/d） 12周诱导衰老，同时在整个研究过程中口服LbGp （100 mg/kg/d）。通过行为试验、心脏超声心动图、病理组织学和转录组学分析评估LbGp的老年保护作用。透射电镜观察线粒体超微结构。采用线粒体应激试验和JC-1荧光探针评价线粒体功能。流式细胞仪和western blot检测细胞自噬通量。结果：LbGp治疗改善了d -半乳糖诱导小鼠的衰老表型，与神经认知和骨骼肌功能相比，心脏功能明显增强。转录组分析表明LbGp改善了心脏的能量代谢。线粒体分析显示，LbGp改善了线粒体功能，并保持了线粒体内膜的结构完整性。LbGp可减弱线粒体分裂，恢复d -半乳糖引起的心肌细胞PINK1/ parkinson介导的线粒体自噬通路受损。结论：LbGp可通过激活d -半乳糖诱导小鼠的PINK1/ parkinson介导的线粒体自噬通路，改善衰老表型，增强心脏代谢。这些发现强调了它作为一种治疗衰老和与衰老相关的心血管疾病的药物的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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