麦角硫因通过cse依赖性过硫化作用增强ccgpdh活性，从而改善老龄动物的健康寿命

IF 27.7 1区生物学 Q1 CELL BIOLOGY

Cell metabolism Pub Date : 2025-01-21 DOI:10.1016/j.cmet.2024.12.008

Dunja Petrovic, Luke Slade, Yiorgos Paikopoulos, Davide D’Andrea, Nevena Savic, Ana Stancic, Jan Lj Miljkovic, Thibaut Vignane, Maria Kyriaki Drekolia, Dusan Mladenovic, Nikola Sutulovic, Alice Refeyton, Milica Kolakovic, Vladimir M. Jovanovic, Jasmina Zivanovic, Marko Miler, Valentina Vellecco, Vincenzo Brancaleone, Mariarosaria Bucci, Alva M. Casey, Milos R. Filipovic

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引用次数: 0

摘要

麦角硫因（ET）是一种膳食硫酮/硫醇，因其在健康衰老和代谢恢复方面的可能益处而受到越来越多的关注。我们的研究调查了ET对老年动物健康寿命的影响，揭示了秀丽隐杆线虫的寿命延长和活动性增强，同时伴随着抗逆性的提高和年龄相关生物标志物的降低。在老年大鼠中，ET可以增强运动耐力、肌肉质量和血管化，同时肌肉中NAD+水平升高。从机制上说，ET作为半胱硫氨酸γ -裂解酶（CSE）的替代底物，刺激H2S的产生，从而增加300多种蛋白质靶点的蛋白质过硫化。其中，蛋白过硫驱动的胞质甘油-3-磷酸脱氢酶（cGPDH）的激活是et诱导的NAD+增加的主要原因。在缺乏CSE或cGPDH的模型中，ET的作用被消除，这突出了H2S信号和蛋白质过硫化的重要作用。这些发现阐明了ET的多方面作用，并为其对抗与年龄相关的肌肉衰退和代谢紊乱的治疗潜力提供了见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Ergothioneine improves healthspan of aged animals by enhancing cGPDH activity through CSE-dependent persulfidation

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Ergothioneine improves healthspan of aged animals by enhancing cGPDH activity through CSE-dependent persulfidation

Ergothioneine (ET), a dietary thione/thiol, is receiving growing attention for its possible benefits in healthy aging and metabolic resilience. Our study investigates ET’s effects on healthspan in aged animals, revealing lifespan extension and enhanced mobility in Caenorhabditis elegans, accompanied by improved stress resistance and reduced age-associated biomarkers. In aged rats, ET administration enhances exercise endurance, muscle mass, and vascularization, concomitant with higher NAD⁺ levels in muscle. Mechanistically, ET acts as an alternative substrate for cystathionine gamma-lyase (CSE), stimulating H₂S production, which increases protein persulfidation of more than 300 protein targets. Among these, protein-persulfidation-driven activation of cytosolic glycerol-3-phosphate dehydrogenase (cGPDH) primarily contributes to the ET-induced NAD⁺ increase. ET’s effects are abolished in models lacking CSE or cGPDH, highlighting the essential role of H₂S signaling and protein persulfidation. These findings elucidate ET’s multifaceted actions and provide insights into its therapeutic potential for combating age-related muscle decline and metabolic perturbations.

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来源期刊

Cell metabolism 生物-内分泌学与代谢

CiteScore

48.60

自引率

1.40%

发文量

173

审稿时长

2.5 months

期刊介绍： Cell Metabolism is a top research journal established in 2005 that focuses on publishing original and impactful papers in the field of metabolic research.It covers a wide range of topics including diabetes, obesity, cardiovascular biology, aging and stress responses, circadian biology, and many others. Cell Metabolism aims to contribute to the advancement of metabolic research by providing a platform for the publication and dissemination of high-quality research and thought-provoking articles.