RT Journal Article
T1 Steroid hormones sulfatase inactivation extends lifespan and ameliorates age-related diseases
A1 Pérez-Jiménez, Mercedes M.
A1 Monje, José Manuel
A1 Brokate Llanos, Ana María
A1 Venegas-Calerón, Mónica
A1 Sánchez-García, Alicia
A1 Sansigre, Paula
A1 Valladares, Amador
A1 Esteban-García, Sara
A1 Suárez-Pereira, Irene
A1 Vitorica, Javier
A1 Ríos, José Julián
A1 Artal-Sanz, Marta
A1 Carrión Rodríguez, Ángel Manuel
A1 Muñoz Ruiz, Manuel Jesús
K1 Aging
K1 Neurodegenerative disease
K1 Sul2
K1 STX64
K1 Proteostasis lost
K1 Alzheimer disease
AB 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.
PB Springer Nature
YR 2021
FD 2021-01-04
LK https://hdl.handle.net/10433/22856
UL https://hdl.handle.net/10433/22856
LA en
NO Pérez-Jiménez, M. M., Monje-Moreno, J. M., Brokate-Llanos, A. M., Venegas-Calerón, M., Sánchez-García, A., Sansigre, P., Valladares, A., Esteban-García, S., Suárez-Pereira, I., Vitorica, J., Ríos, J. J., Artal-Sanz, M., Carrión, Á. M., & Muñoz, M. J. (2021). Steroid hormones sulfatase inactivation extends lifespan and ameliorates age-related diseases. Nature Communications, 12(1), 49–49. https://doi.org/10.1038/s41467-020-20269-y
NO Dpto Fisiología, Anatomía y Biología Celular, Universidad Pablo de Olavide
NO Dpto Genetica, Universidad Pablo de Olavide
NO Centro Andaluz de Biología del Desarrollo (CABD), CSIC
NO Dpto de Bioquímica, fac. Farmacia, Universidad de Sevilla
NO Instituto de la Grasa (CSIC)
DS RIO
RD May 9, 2026