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Steroid hormones sulfatase inactivation extends lifespan and ameliorates age-related diseases

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dc.contributor.authorPérez-Jiménez, Mercedes M.
dc.contributor.authorMonje-Moreno, José M.
dc.contributor.authorBrokate-Llanos, Ana María
dc.contributor.authorVenegas-Calerón, Mónica
dc.contributor.authorSánchez-García, Alicia
dc.contributor.authorSansigre, Paula
dc.contributor.authorValladares, Amador
dc.contributor.authorEsteban-García, Sara
dc.contributor.authorSuárez-Pereira, Irene
dc.contributor.authorVitorica, Javier
dc.contributor.authorRíos, José Julián
dc.contributor.authorArtal-Sanz, Marta
dc.contributor.authorCarrión, Ángel M.
dc.contributor.authorMuñoz, Manuel J.
dc.contributor.authoraffiliation[Pérez-Jiménez,MM; Monje-Moreno,JM; Brokate-Llanos,AM; Sansigre,P; Valladares,A; Artal-Sanz,M; Muñoz,MJ] Centro Andaluz de Biología del Desarrollo (CABD)—Universidad Pablo de Olavide (UPO), Departamento de Biología Molecular e Ingeniería Bioquímica, UPO/ CSIC/JA, Sevilla, Spain. [Venegas-Calerón,M; Sánchez-García,A; Ríos,JJ] Instituto de la Grasa (CSIC), Campus Universitario Pablo de Olavide (UPO), Sevilla, Spain. [Esteban-García,S; Suárez-Pereira,I; Carrión,AM] Departamento de Fisiología, Anatomía y Biología Celular, Universidad Pablo de Olavide (UPO), Sevilla, Spain. [Vitorica,J] Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, Sevilla, Spain. [Vitorica,J] Instituto de Biomedicina de Sevilla (IBiS)-Hospital Universitario Virgen del Rocío/ CSIC/Universidad de Sevilla, Sevilla, Spain. [Vitorica,J] Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain. [Suárez-Pereira,I] Europsychopharmacology and psychobiology research group, Universidad de Cadiz, CIBERSAM, INiBICA, Cadiz, Spain.
dc.contributor.funderThis work was supported by the Junta de Andalucía Project P07-CVI-02697, “Fondo Europeo de Desarrollo Regional” (FEDER) and the “Consejería de Economía, Conocimiento, Empresas y Universidad, Junta de Andalucía” Project UPO-1266266 and the European Research Council ERC-2011-StG-281691. We also acknowledge the support from the Centro Andaluz de Biología del Desarrollo (CABD).
dc.date.accessioned2022-10-31T12:08:39Z
dc.date.available2022-10-31T12:08:39Z
dc.date.issued2021-01-04
dc.description.abstractAging and fertility are two interconnected processes. From invertebrates to mammals, absence of the germline increases longevity. Here we show that loss of function of sul-2, the Caenorhabditis elegans steroid sulfatase (STS), raises the pool of sulfated steroid hormones, increases longevity and ameliorates protein aggregation diseases. This increased longevity requires factors involved in germline-mediated longevity (daf-16, daf-12, kri-1, tcer-1 and daf-36 genes) although sul-2 mutations do not affect fertility. Interestingly, sul-2 is only expressed in sensory neurons, suggesting a regulation of sulfated hormones state by environmental cues. Treatment with the specific STS inhibitor STX64, as well as with testosterone-derived sulfated hormones reproduces the longevity phenotype of sul-2 mutants. Remarkably, those treatments ameliorate protein aggregation diseases in C. elegans, and STX64 also Alzheimer's disease in a mammalian model. These results open the possibility of reallocating steroid sulfatase inhibitors or derivates for the treatment of aging and aging related diseases.es_ES
dc.description.versionYeses_ES
dc.identifier.citationPérez-Jiménez MM, Monje-Moreno JM, Brokate-Llanos AM, Venegas-Calerón M, Sánchez-García A, Sansigre P, et al. Steroid hormones sulfatase inactivation extends lifespan and ameliorates age-related diseases. Nat Commun. 2021 Jan 4;12(1):49es_ES
dc.identifier.doi10.1038/s41467-020-20269-yes_ES
dc.identifier.essn2041-1723
dc.identifier.pmcPMC7782729
dc.identifier.pmid33397961es_ES
dc.identifier.urihttp://hdl.handle.net/10668/4311
dc.journal.titleNature Communications
dc.language.isoen
dc.page.number12 p.
dc.publisherNature Publishing Groupes_ES
dc.relation.publisherversionhttps://www.nature.com/articles/s41467-020-20269-yes_ES
dc.rightsAtribución 4.0 Internacional*
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectLongevityes_ES
dc.subjectAlzheimer diseasees_ES
dc.subjectFertilityes_ES
dc.subjectAginges_ES
dc.subjectMutationes_ES
dc.subjectSensory neuronses_ES
dc.subjectPhenotypees_ES
dc.subjectTestosteronees_ES
dc.subjectSteroidses_ES
dc.subjectSulfataseses_ES
dc.subjectLongevidades_ES
dc.subjectEnfermedad de alzheimeres_ES
dc.subjectFertilidades_ES
dc.subjectEnvejecimientoes_ES
dc.subjectMutaciónes_ES
dc.subjectCélulas receptoras sensorialeses_ES
dc.subjectFenotipoes_ES
dc.subjectTestosteronaes_ES
dc.subjectEsteroideses_ES
dc.subjectSulfatasases_ES
dc.subject.meshMedical Subject Headings::Diseases::Nervous System Diseases::Neurodegenerative Diseases::Tauopathies::Alzheimer Diseasees_ES
dc.subject.meshMedical Subject Headings::Organisms::Eukaryota::Animalses_ES
dc.subject.meshMedical Subject Headings::Organisms::Eukaryota::Animals::Invertebrates::Helminths::Nematoda::Secernentea::Rhabditida::Rhabditoidea::Caenorhabditis::Caenorhabditis eleganses_ES
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Helminth Proteins::Caenorhabditis elegans Proteinses_ES
dc.subject.meshMedical Subject Headings::Diseases::Animal Diseases::Disease Models, Animales_ES
dc.subject.meshMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Epistasis, Genetices_ES
dc.subject.meshMedical Subject Headings::Anatomy::Urogenital System::Genitalia::Gonadses_ES
dc.subject.meshMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Micees_ES
dc.subject.meshMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Phenotypees_ES
dc.subject.meshMedical Subject Headings::Anatomy::Cells::Neurons::Neurons, Afferent::Sensory Receptor Cellses_ES
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Polycyclic Compounds::Steroidses_ES
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Esterases::Sulfatases::Arylsulfatases::Steryl-Sulfatasees_ES
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Esterases::Sulfataseses_ES
dc.subject.meshMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Longevityes_ES
dc.subject.meshMedical Subject Headings::Psychiatry and Psychology::Psychological Phenomena and Processes::Mental Processes::Learning::Cueses_ES
dc.subject.meshMedical Subject Headings::Anatomy::Cells::Germ Cellses_ES
dc.subject.meshMedical Subject Headings::Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Fertilityes_ES
dc.subject.meshMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutationes_ES
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Gonadal Hormones::Gonadal Steroid Hormones::Testosterone Congeners::Testosteronees_ES
dc.subject.meshMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammalses_ES
dc.titleSteroid hormones sulfatase inactivation extends lifespan and ameliorates age-related diseaseses_ES
dc.typeresearch article
dc.type.hasVersionVoR
dspace.entity.typePublication

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