Steroid hormones sulfatase inactivation extends lifespan and ameliorates age-related diseases

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 and Manuel J. Muñoz ()
Additional contact information
Mercedes M. Pérez-Jiménez: Centro Andaluz de Biología del Desarrollo (CABD)—Universidad Pablo de Olavide (UPO), Departamento de Biología Molecular e Ingeniería Bioquímica, UPO/ CSIC/JA
José M. Monje-Moreno: Centro Andaluz de Biología del Desarrollo (CABD)—Universidad Pablo de Olavide (UPO), Departamento de Biología Molecular e Ingeniería Bioquímica, UPO/ CSIC/JA
Ana María Brokate-Llanos: Centro Andaluz de Biología del Desarrollo (CABD)—Universidad Pablo de Olavide (UPO), Departamento de Biología Molecular e Ingeniería Bioquímica, UPO/ CSIC/JA
Mónica Venegas-Calerón: Campus Universitario Pablo de Olavide (UPO)
Alicia Sánchez-García: Campus Universitario Pablo de Olavide (UPO)
Paula Sansigre: Centro Andaluz de Biología del Desarrollo (CABD)—Universidad Pablo de Olavide (UPO), Departamento de Biología Molecular e Ingeniería Bioquímica, UPO/ CSIC/JA
Amador Valladares: Centro Andaluz de Biología del Desarrollo (CABD)—Universidad Pablo de Olavide (UPO), Departamento de Biología Molecular e Ingeniería Bioquímica, UPO/ CSIC/JA
Sara Esteban-García: Universidad Pablo de Olavide (UPO)
Irene Suárez-Pereira: Universidad Pablo de Olavide (UPO)
Javier Vitorica: Universidad de Sevilla
José Julián Ríos: Campus Universitario Pablo de Olavide (UPO)
Marta Artal-Sanz: Centro Andaluz de Biología del Desarrollo (CABD)—Universidad Pablo de Olavide (UPO), Departamento de Biología Molecular e Ingeniería Bioquímica, UPO/ CSIC/JA
Ángel M. Carrión: Universidad Pablo de Olavide (UPO)
Manuel J. Muñoz: Centro Andaluz de Biología del Desarrollo (CABD)—Universidad Pablo de Olavide (UPO), Departamento de Biología Molecular e Ingeniería Bioquímica, UPO/ CSIC/JA

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-020-20269-y

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