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, accomp...

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Detalles Bibliográficos
Autores: Petrovic, Dunja, Slade, Luke, Paikopoulos, Yiorgos, D'Andrea, Davide, Savic, Nevena, Stancic, Ana, Miljkovic, Jan Lj, Vignane, Thibaut, Drekolia, Maria Kyriaki, Mladenovic, Dusan, Sutulovic, Nikola, Refeyton, Alice, Kolakovic, Milica, Jovanovic, Vladimir, Zivanovic, Jasmina, Miler, Marko, Vellecco, Valentina, Brancaleone, Vincenzo, Bucci, Mariarosaria, Casey, Alva M., Yu, ChakShun, Kasarla, Siva Swapna, Smith, Karl William, Kalfe-Yildiz, Ayten, Stenzel, Martin, Miranda-Vizuete, Antonio, Hergenröder, Roland, Phapale, Prasad, Stanojlovic, Olivera, Ivanovic-Burmazovic, Ivana, Vlaski-Lafarge, Marija, Bibli, Sofia-Iris, Murphy, Michael P., Otasevic, Vesna, Filipovic, Milos R.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/390932
Acceso en línea:http://hdl.handle.net/10261/390932
https://api.elsevier.com/content/abstract/scopus_id/85216298824
Access Level:acceso abierto
Palabra clave:NAD
Ergothioneine
Healthspan
Hydrogen sulfide
Persulfidation
Descripción
Sumario: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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