Reference - Detail
| RRC ID | 65371 |
|---|---|
| Author | Pérez-Jiménez MM, Monje-Moreno JM, Brokate-Llanos AM, Venegas-Calerón M, Sánchez-García A, Sansigre P, Valladares A, Esteban-García S, Suárez-Pereira I, Vitorica J, Ríos JJ, Artal-Sanz M, Carrión ÁM, Muñoz MJ. |
| Title | Steroid hormones sulfatase inactivation extends lifespan and ameliorates age-related diseases. |
| Journal | Nat Commun |
| Abstract |
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. |
| Volume | 12(1) |
| Pages | 49 |
| Published | 2021-1-4 |
| DOI | 10.1038/s41467-020-20269-y |
| PII | 10.1038/s41467-020-20269-y |
| PMID | 33397961 |
| PMC | PMC7782729 |
| MeSH | Alzheimer Disease / enzymology* Alzheimer Disease / pathology* Animals Caenorhabditis elegans / enzymology* Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / metabolism* Disease Models, Animal Epistasis, Genetic Gonads / metabolism Longevity* Mice Phenotype Sensory Receptor Cells / metabolism Steroids / metabolism Steryl-Sulfatase / metabolism* Sulfatases / metabolism* |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 105 |
| Altmetric score changes over past 6months | 3.0 |
| Resource | |
| C.elegans | tm6179 tm1452 tm1011 |