College of Food Science & Institute of Food Biotechnology, South China Agricultural University, Guangzhou 510640, China.
Research Center for Micro-Ecological Agent Engineering and Technology of Guangdong Province, Guangzhou 510640, China.
Food Funct. 2022 Jan 4;13(1):227-241. doi: 10.1039/d1fo02758a.
Many studies have demonstrated the protective effect of ergothioneine (EGT), the unique sulfur-containing antioxidant found in mushrooms, on several aging-related diseases. Nevertheless, to date, no single study has explored the potential role of EGT in the lifespan of animal models. We show here that EGT consistently extends fly lifespan in diverse genetic backgrounds and both sexes, as well as in a dose and gender-dependent manner. Additionally, EGT is shown to increases the climbing activity of flies, enhance acetylcholinesterase (AchE) activity, and maintain the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG)of aged flies. The increase in lifespan by EGT is gut microorganism dependent. We proposed potential mechanisms of lifespan extension in by EGT through RNA-seq analysis: preservation of the normal status of the central nervous system the coordination of cholinergic neurotransmission, tyrosine metabolism, and peroxisomal proteins, regulation of autophagic activity by altering the lysosomal protein CTSD, and the preservation of normal mitochondrial function through controlled substrate feeding into the tricarboxylic acid (TCA) cycle, the major energy-yielding metabolic process in cells.
许多研究表明，真菌中独有的含硫抗氧化剂——麦硫因（EGT）对多种与衰老相关的疾病具有保护作用。然而，迄今为止，尚无单一研究探讨 EGT 在动物模型寿命中的潜在作用。我们在这里表明，EGT 可在不同遗传背景和性别中一致延长果蝇的寿命，且具有剂量和性别依赖性。此外，EGT 可增加果蝇的攀爬活动、提高乙酰胆碱酯酶（AchE）活性，并维持老年果蝇中还原型谷胱甘肽（GSH）与氧化型谷胱甘肽（GSSG）的比值。EGT 对寿命的延长依赖于肠道微生物群。我们通过 RNA-seq 分析提出了 EGT 延长寿命的潜在机制：通过改变溶酶体蛋白 CTSD 来调节自噬活性，从而维持中枢神经系统的正常状态，协调胆碱能神经递质、酪氨酸代谢和过氧化物酶体蛋白的协调作用，以及通过控制三羧酸（TCA）循环中的底物进料来维持正常的线粒体功能，TCA 循环是细胞中主要的产能代谢过程。
