Enhanced non-enzymatic H2S generation extends lifespan and healthspan in male mice
Year: 2025
Type: article
Abstract: 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.
Source: Cell Metabolism
Authors: María Ángeles Cáliz-Molina, Raúl López-Fernández-Sobrino, Inmaculada Pino-Pérez, Concepción Panadero-Morón, María del Carmen Vilches-Pérez, María Camacho-Cabrera, Almudena García-Ruiz, Leopoldo Pérez-Rosendo, Isabel Espadas, Alejandro Sola-García, Mario Soriano-Navarro, Franz Martin, Mónica Venegas-Calerón, Joaquín Jesús Salas, Enrique Martínez-Force, Luis C. Romero, Ángeles Aroca, Román González-Prieto, Máximo Bernabeu-Wittel, Vivian Capilla-González, Christopher Hine, Alejandro Martín-Montalvo
Institutions: Centro Andaluz de Biología Molecular y Medicina Regenerativa, Universidad de Sevilla, Universidad Pablo de Olavide, Centro de Investigacion Principe Felipe, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas, Centro de Investigación Biomédica en Red, Consejo Superior de Investigaciones Científicas, Instituto de la Grasa, Instituto de Bioquímica Vegetal y Fotosíntesis, Hospital Universitario Virgen del Rocío, Cleveland Clinic, Cleveland Clinic Lerner College of Medicine
Language: English
Topic: Sulfur Compounds in Biology
Subfield: Biochemistry
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $10,400
Funders: Ministerio de Ciencia, Innovación y Universidades, Ministerio de Ciencia e Innovación, Junta de Andalucía, Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas, Consejo Superior de Investigaciones Científicas, Instituto de Salud Carlos III, Sociedad Española de Diabetes, Consejería de Salud y Consumo, Junta de Andalucía
OpenAlex ID: W4417505337