Steroid hormones sulfatase inactivation extends lifespan and ameliorates age-related diseases
| Autor: | José Ríos, Amador Valladares, Irene Suárez-Pereira, Mónica Venegas-Calerón, José M. Monje-Moreno, Paula Sansigre, Sara Esteban-García, Marta Artal-Sanz, Manuel Muñoz, Javier Vitorica, Angel M. Carrión, Alicia Sánchez-García, Ana María Brokate-Llanos, Mercedes M. Pérez-Jiménez |
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| Přispěvatelé: | Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular, Junta de Andalucía, European Coal and Steel Community, European Research Council, [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., This 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). |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Aging Chemicals and Drugs::Amino Acids Peptides and Proteins::Proteins::Helminth Proteins::Caenorhabditis elegans Proteins [Medical Subject Headings] Phenomena and Processes::Genetic Phenomena::Phenotype [Medical Subject Headings] medicine.medical_treatment Envejecimiento General Physics and Astronomy Phenomena and Processes::Physiological Phenomena::Longevity [Medical Subject Headings] Protein aggregation Psychiatry and Psychology::Psychological Phenomena and Processes::Mental Processes::Learning::Cues [Medical Subject Headings] Mice 0302 clinical medicine Anatomy::Urogenital System::Genitalia::Gonads [Medical Subject Headings] Organisms::Eukaryota::Animals [Medical Subject Headings] Testosterone Testosterona Caenorhabditis elegans media_common Multidisciplinary biology Sulfatase Anatomy::Cells::Neurons::Neurons Afferent::Sensory Receptor Cells [Medical Subject Headings] Chemicals and Drugs::Hormones Hormone Substitutes and Hormone Antagonists::Hormones::Gonadal Hormones::Gonadal Steroid Hormones::Testosterone Congeners::Testosterone [Medical Subject Headings] Longevity Phenotype Cell biology Esteroides Steroids Sulfatases Fenotipo Sulfatasas Sensory neurons Diseases::Nervous System Diseases::Neurodegenerative Diseases::Tauopathies::Alzheimer Disease [Medical Subject Headings] Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation [Medical Subject Headings] Phenotypic screening Sensory Receptor Cells Science media_common.quotation_subject Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Fertility [Medical Subject Headings] General Biochemistry Genetics and Molecular Biology Article Steroid 03 medical and health sciences Alzheimer Disease Anatomy::Cells::Germ Cells [Medical Subject Headings] parasitic diseases Steroid sulfatase medicine Animals Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Esterases::Sulfatases::Arylsulfatases::Steryl-Sulfatase [Medical Subject Headings] Caenorhabditis elegans Proteins Gonads Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals [Medical Subject Headings] Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice [Medical Subject Headings] Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Esterases::Sulfatases [Medical Subject Headings] Enfermedad de alzheimer Mutación Chemicals and Drugs::Polycyclic Compounds::Steroids [Medical Subject Headings] fungi Epistasis Genetic General Chemistry Organisms::Eukaryota::Animals::Invertebrates::Helminths::Nematoda::Secernentea::Rhabditida::Rhabditoidea::Caenorhabditis::Caenorhabditis elegans [Medical Subject Headings] biology.organism_classification Diseases::Animal Diseases::Disease Models Animal [Medical Subject Headings] Ageing Disease Models Animal 030104 developmental biology Fertility Fertilidad Longevidad Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Epistasis Genetic [Medical Subject Headings] Mutation Steryl-Sulfatase Células receptoras sensoriales 030217 neurology & neurosurgery Hormone |
| Zdroj: | idUS: Depósito de Investigación de la Universidad de Sevilla Universidad de Sevilla (US) Nature Communications Digital.CSIC. Repositorio Institucional del CSIC instname Nature Communications, Vol 12, Iss 1, Pp 1-12 (2021) idUS. Depósito de Investigación de la Universidad de Sevilla |
| Popis: | 12 Páginas.-- 5 Figuras Aging 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. We thank the CGC. A. Miranda-Vizuete and J. Alcedo for providing strains; Y. Kohara and P. Askjaer for DNA clones; A. Garzón, P. Askjaer and M. Vanghell for critical review of the manuscript; A. P. Pulido for bioinformatic advices; V. Carranco for his excellent technical assistance during whole project, and also A. López, A. Cano, V. Rubio, S. Romero and E. Gara for their technical support; and K. Garcia for microscopy assistance. This 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). |
| Databáze: | OpenAIRE |
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