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...
| Autores: | , , , , , , , , , , , , , , , , , , , , , |
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| 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 |
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Enhanced non-enzymatic H2S generation extends lifespan and healthspan in male miceCáliz-Molina, María ÁngelesLópez-Fernández-Sobrino, RaúlPino-Pérez, InmaculadaPanadero-Morón, ConcepciónVilches-Pérez, María Del CarmenCamacho-Cabrera, MaríaGarcía-Ruiz, AlmudenaPérez-Rosendo, LeopoldoEspadas, IsabelSola-García, AlejandroSoriano-Navarro, MarioMartin, FranzVenegas-Calerón, MónicaSalas, Joaquín JesúsMartínez-Force, EnriqueRomero, Luis C.Aroca, ÁngelesGonzález-Prieto, RománBernabeu-Wittel, MáximoCapilla-González, VivianHine, ChristopherMartín-Montalvo, AlejandroDiallyl disulfideDiallyl trisulfideGarlicGeroprotectorHydrogen sulfideHealthspanLifespanLongevityPersulfidationHydrogen 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.Ministerio de Ciencia e InnovaciónJunta de Andalucíathe Spanish Society of DiabetesAgencia Estatal de Investigaciónthe Institute of Health Carlos IIIPeer reviewedModelo experimental animalMamíferos - RoedoresCell PressMinisterio de Ciencia e Innovación (España)Junta de AndalucíaEuropean CommissionConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202620262026info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/421301https://api.elsevier.com/content/abstract/scopus_id/105025376717reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttps://doi.org/10.1016/j.cmet.2025.11.012Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/4213012026-05-22T06:33:51Z |
| dc.title.none.fl_str_mv |
Enhanced non-enzymatic H2S generation extends lifespan and healthspan in male mice |
| title |
Enhanced non-enzymatic H2S generation extends lifespan and healthspan in male mice |
| spellingShingle |
Enhanced non-enzymatic H2S generation extends lifespan and healthspan in male mice Cáliz-Molina, María Ángeles Diallyl disulfide Diallyl trisulfide Garlic Geroprotector Hydrogen sulfide Healthspan Lifespan Longevity Persulfidation |
| title_short |
Enhanced non-enzymatic H2S generation extends lifespan and healthspan in male mice |
| title_full |
Enhanced non-enzymatic H2S generation extends lifespan and healthspan in male mice |
| title_fullStr |
Enhanced non-enzymatic H2S generation extends lifespan and healthspan in male mice |
| title_full_unstemmed |
Enhanced non-enzymatic H2S generation extends lifespan and healthspan in male mice |
| title_sort |
Enhanced non-enzymatic H2S generation extends lifespan and healthspan in male mice |
| dc.creator.none.fl_str_mv |
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 |
| author |
Cáliz-Molina, María Ángeles |
| author_facet |
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 |
| author_role |
author |
| author2 |
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 |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Ministerio de Ciencia e Innovación (España) Junta de Andalucía European Commission Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72] |
| dc.subject.none.fl_str_mv |
Diallyl disulfide Diallyl trisulfide Garlic Geroprotector Hydrogen sulfide Healthspan Lifespan Longevity Persulfidation |
| topic |
Diallyl disulfide Diallyl trisulfide Garlic Geroprotector Hydrogen sulfide Healthspan Lifespan Longevity Persulfidation |
| description |
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. |
| publishDate |
2026 |
| dc.date.none.fl_str_mv |
2026 2026 2026 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article http://purl.org/coar/resource_type/c_6501 Publisher's version info:eu-repo/semantics/publishedVersion |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10261/421301 https://api.elsevier.com/content/abstract/scopus_id/105025376717 |
| url |
http://hdl.handle.net/10261/421301 https://api.elsevier.com/content/abstract/scopus_id/105025376717 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
https://doi.org/10.1016/j.cmet.2025.11.012 Sí |
| dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess |
| eu_rights_str_mv |
openAccess |
| dc.publisher.none.fl_str_mv |
Cell Press |
| publisher.none.fl_str_mv |
Cell Press |
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reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC instname:Consejo Superior de Investigaciones Científicas (CSIC) |
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Consejo Superior de Investigaciones Científicas (CSIC) |
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DIGITAL.CSIC. Repositorio Institucional del CSIC |
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DIGITAL.CSIC. Repositorio Institucional del CSIC |
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1869405389890519040 |
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15,811543 |