Enhanced non-enzymatic H2S generation extends lifespan and healthspan in male mice

Hydrogen sulfide is a gasotransmitter with biological functions, including roles in antioxidant defenses, mitochondrial bioenergetics, and cellular signaling via cysteine persulfidation. Several longevity-promoting interventions enhance endogenous hydrogen sulfide generation. However, whether enhanc...

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Detalles Bibliográficos
Autores: Cáliz-Molina, María Ángeles, López-Fernández-Sobrino, Raúl, Pino-Pérez, Inmaculada, Panadero-Morón, Concepción, Vilches-Pérez, María Del Carmen, Camacho-Cabrera, María, García-Ruiz, Almudena, Pérez-Rosendo, Leopoldo, Espadas, Isabel, Sola-García, Alejandro, Soriano-Navarro, Mario, Martin, Franz, Venegas-Calerón, Mónica, Salas, Joaquín Jesús, Martínez-Force, Enrique, Romero, Luis C., Aroca, Ángeles, González-Prieto, Román, Bernabeu-Wittel, Máximo, Capilla-González, Vivian, Hine, Christopher, Martín-Montalvo, Alejandro
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2026
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/421301
Acceso en línea:http://hdl.handle.net/10261/421301
https://api.elsevier.com/content/abstract/scopus_id/105025376717
Access Level:acceso abierto
Palabra clave:Diallyl disulfide
Diallyl trisulfide
Garlic
Geroprotector
Hydrogen sulfide
Healthspan
Lifespan
Longevity
Persulfidation
Descripción
Sumario:Hydrogen sulfide is a gasotransmitter with biological functions, including roles in antioxidant defenses, mitochondrial bioenergetics, and cellular signaling via cysteine persulfidation. Several longevity-promoting interventions enhance endogenous hydrogen sulfide generation. However, whether enhanced hydrogen sulfide generation extends healthspan and lifespan in mammals remains unknown. Here, we investigated the in vivo effects of the non-enzymatic hydrogen sulfide generation promoted by natural diallyl sulforated compounds. Diallyl sulforated compounds extended lifespan and improved the main aspects of healthspan, including glucoregulation, locomotor function, and neurocognition in wild-type male mice across their lifespan. At the histological and molecular levels, we observed reductions in hepatic lipid-droplet size, attenuation of transcriptional and proteomic signatures associated with mTOR and immune-related pathways, and increased cysteine persulfidation in proteins. In humans, greater protein persulfidation in individuals with polypathological conditions was associated with increased muscle strength and lower triglyceride levels, supporting its physiological relevance. Our findings uncover the potential of enhanced hydrogen sulfide generation to promote healthy aging.

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