德国莱布尼茨分析科学研究所Milos R. Filipovic团队发现，麦角硫因通过CSE依赖性过硫酸化作用增强cGPDH活性来改善老年动物的健康寿命。该项研究成果于2025年1月21日在线发表在《细胞—代谢》上。

研究人员探讨了麦角硫因（ET）对老年动物健康寿命的影响，揭示了在秀丽隐杆线虫中延长了寿命并增强了运动能力，同时伴随着改善的抗压能力和减少的与年龄相关的生物标志物。在老年大鼠中，ET的施用提高了运动耐力、肌肉质量和血管化，同时肌肉中的NAD⁺水平也有所升高。

从机制上讲，ET作为半胱氨酸γ-裂解酶（CSE）的替代底物，刺激了H₂S的产生，从而增加了超过300个蛋白质靶点的过硫酸化修饰。在这些靶点中，蛋白质过硫酸化驱动的细胞质甘油-3-磷酸脱氢酶（cGPDH）激活主要促进了ET引起的NAD⁺增加。在缺乏CSE或cGPDH的模型中，ET的效果被完全消除，突出了H₂S信号传导和蛋白质过硫酸化在这一过程中的关键作用。

这些发现阐明了ET的多方面作用，并为其在对抗与年龄相关的肌肉衰退和代谢紊乱方面的治疗潜力提供了新的见解。

据悉，ET是一种膳食硫氨/硫醇，因其可能对健康衰老和代谢适应性具有益处而受到越来越多的关注。

附：英文原文

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

Author: 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, ChakShun Yu, Siva Swapna Kasarla, Karl William Smith, Ayten Kalfe-Yildiz, Martin Stenzel, Antonio Miranda-Vizuete, Roland Hergenrder, Prasad Phapale, Olivera Stanojlovic, Ivana Ivanovic-Burmazovic, Marija Vlaski-Lafarge, Sofia-Iris Bibli, Michael P. Murphy, Vesna Otasevic, Milos R. Filipovic

Issue&Volume: 2025-01-21

Abstract: 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.

DOI: 10.1016/j.cmet.2024.12.008

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(24)00490-X