Downloads provided by UsageCountsSteroid hormones sulfatase inactivation extends lifespan and ameliorates age-related diseases
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Mercedes M. Pérez-Jiménez; José M. Monje-Moreno; Ana María Brokate-Llanos; Mónica Venegas-Calerón; Alicia Sánchez-García; Paula Sansigre; Amador Valladares; +7 Authors
Mercedes M. Pérez-Jiménez; José M. Monje-Moreno; Ana María Brokate-Llanos; Mónica Venegas-Calerón; Alicia Sánchez-García; Paula Sansigre; Amador Valladares; Sara Esteban-García; Irene Suárez-Pereira; Javier Vitorica; José Julián Ríos; Marta Artal-Sanz; Ángel M. Carrión; Manuel J. Muñoz;
Steroid hormones sulfatase inactivation extends lifespan and ameliorates age-related diseases
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.
Aging, Medical Subject Headings::Anatomy::Cells::Neurons::Neurons, Afferent::Sensory Receptor Cells, Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation, Sensory Receptor Cells, Science, Longevity, Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Esterases::Sulfatases, Medical Subject Headings::Phenomena and Processes::Physiological Phenomena::Longevity, STX64, Medical Subject Headings::Anatomy::Cells::Germ Cells, Neurodegenerative disease, Medical Subject Headings::Psychiatry and Psychology::Psychological Phenomena and Processes::Mental Processes::Learning::Cues, Article, Medical Subject Headings::Organisms::Eukaryota::Animals::Invertebrates::Helminths::Nematoda::Secernentea::Rhabditida::Rhabditoidea::Caenorhabditis::Caenorhabditis elegans, Mice, Alzheimer Disease, Medical Subject Headings::Diseases::Nervous System Diseases::Neurodegenerative Diseases::Tauopathies::Alzheimer Disease, Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Gonads, Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Epistasis, Genetic, Medical Subject Headings::Chemicals and Drugs::Polycyclic Compounds::Steroids, Proteostasis lost, Q, Medical Subject Headings::Diseases::Animal Diseases::Disease Models, Animal, Sul2, Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice, Epistasis, Genetic, Medical Subject Headings::Anatomy::Urogenital System::Genitalia::Gonads, Medical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Gonadal Hormones::Gonadal Steroid Hormones::Testosterone Congeners::Testosterone, Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals, Medical Subject Headings::Organisms::Eukaryota::Animals, Disease Models, Animal, Phenotype, Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Phenotype, Steroids, Steryl-Sulfatase, Alzheimer disease, Sulfatases, Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Helminth Proteins::Caenorhabditis elegans Proteins, Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Esterases::Sulfatases::Arylsulfatases::Steryl-Sulfatase, Medical Subject Headings::Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Fertility
Aging, Medical Subject Headings::Anatomy::Cells::Neurons::Neurons, Afferent::Sensory Receptor Cells, Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation, Sensory Receptor Cells, Science, Longevity, Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Esterases::Sulfatases, Medical Subject Headings::Phenomena and Processes::Physiological Phenomena::Longevity, STX64, Medical Subject Headings::Anatomy::Cells::Germ Cells, Neurodegenerative disease, Medical Subject Headings::Psychiatry and Psychology::Psychological Phenomena and Processes::Mental Processes::Learning::Cues, Article, Medical Subject Headings::Organisms::Eukaryota::Animals::Invertebrates::Helminths::Nematoda::Secernentea::Rhabditida::Rhabditoidea::Caenorhabditis::Caenorhabditis elegans, Mice, Alzheimer Disease, Medical Subject Headings::Diseases::Nervous System Diseases::Neurodegenerative Diseases::Tauopathies::Alzheimer Disease, Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Gonads, Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Epistasis, Genetic, Medical Subject Headings::Chemicals and Drugs::Polycyclic Compounds::Steroids, Proteostasis lost, Q, Medical Subject Headings::Diseases::Animal Diseases::Disease Models, Animal, Sul2, Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice, Epistasis, Genetic, Medical Subject Headings::Anatomy::Urogenital System::Genitalia::Gonads, Medical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Gonadal Hormones::Gonadal Steroid Hormones::Testosterone Congeners::Testosterone, Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals, Medical Subject Headings::Organisms::Eukaryota::Animals, Disease Models, Animal, Phenotype, Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Phenotype, Steroids, Steryl-Sulfatase, Alzheimer disease, Sulfatases, Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Helminth Proteins::Caenorhabditis elegans Proteins, Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Esterases::Sulfatases::Arylsulfatases::Steryl-Sulfatase, Medical Subject Headings::Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Fertility
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This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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