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

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...

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Main Authors: Petrovic, Dunja (Author) , Slade, Luke (Author) , Paikopoulos, Yiorgos (Author) , D’Andrea, Davide (Author) , Savic, Nevena (Author) , Stancic, Ana (Author) , Miljkovic, Jan Lj (Author) , Vignane, Thibaut (Author) , Drekolia, Maria-Kyriaki (Author) , Mladenovic, Dusan (Author) , Sutulovic, Nikola (Author) , Refeyton, Alice (Author) , Kolakovic, Milica (Author) , Jovanovic, Vladimir M. (Author) , Zivanovic, Jasmina (Author) , Miler, Marko (Author) , Vellecco, Valentina (Author) , Brancaleone, Vincenzo (Author) , Bucci, Mariarosaria (Author) , Casey, Alva M. (Author) , Yu, ChakShun (Author) , Kasarla, Siva Swapna (Author) , Smith, Karl William (Author) , Kalfe-Yildiz, Ayten (Author) , Stenzel, Martin (Author) , Miranda-Vizuete, Antonio (Author) , Hergenröder, Roland (Author) , Phapale, Prasad (Author) , Stanojlovic, Olivera (Author) , Ivanovic-Burmazovic, Ivana (Author) , Vlaski-Lafarge, Marija (Author) , Bibli, Sofia-Iris (Author) , Murphy, Michael P. (Author) , Otasevic, Vesna (Author) , Filipovic, Milos R. (Author)
Format: Article (Journal)
Language:English
Published: 4 February 2025
In: Cell metabolism
Year: 2025, Volume: 37, Issue: 2, Pages: 542-556.e14
ISSN:1932-7420
DOI:10.1016/j.cmet.2024.12.008
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.cmet.2024.12.008
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S155041312400490X
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Author Notes: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 Hergenröder, Prasad Phapale, Olivera Stanojlovic, Ivana Ivanovic-Burmazovic, Marija Vlaski-Lafarge, Sofia-Iris Bibli, Michael P. Murphy, Vesna Otasevic, and Milos R. Filipovic
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Summary: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.
Item Description:Online verfügbar: 21. Januar 2025, Artikelversion: 4. Februar 2025
Gesehen am 17.07.2025
Physical Description:Online Resource
ISSN:1932-7420
DOI:10.1016/j.cmet.2024.12.008

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