| 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*
|
| Resource |
| C.elegans |
tm6179
tm1452
tm1011 |
