RT Journal Article
T1 Steroid hormones sulfatase inactivation extends lifespan and ameliorates age-related diseases
A1 Pérez-Jiménez, Mercedes M.
A1 Monje-Moreno, José M.
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, Ángel M.
A1 Muñoz, Manuel J.
K1 Longevity
K1 Alzheimer disease
K1 Fertility
K1 Aging
K1 Mutation
K1 Sensory neurons
K1 Phenotype
K1 Testosterone
K1 Steroids
K1 Sulfatases
K1 Longevidad
K1 Enfermedad de alzheimer
K1 Fertilidad
K1 Envejecimiento
K1 Mutación
K1 Células receptoras sensoriales
K1 Fenotipo
K1 Testosterona
K1 Esteroides
K1 Sulfatasas
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 Nature Publishing Group
YR 2021
FD 2021-01-04
LK http://hdl.handle.net/10668/4311
UL http://hdl.handle.net/10668/4311
LA en
NO Pérez-Jiménez MM, Monje-Moreno JM, Brokate-Llanos AM, Venegas-Calerón M, Sánchez-García A, Sansigre P, et al. Steroid hormones sulfatase inactivation extends lifespan and ameliorates age-related diseases. Nat Commun. 2021 Jan 4;12(1):49
DS RISalud
RD Apr 9, 2025