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

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  • 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)
    Universidad de Cadiz, CIBERSAM, INiBICA)

  • Javier Vitorica

    (Universidad de Sevilla
    Instituto de Biomedicina de Sevilla (IBiS)-Hospital Universitario Virgen del Rocío/ CSIC/Universidad de Sevilla
    Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED))

  • 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)

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.

Suggested Citation

  • 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-P, 2021. "Steroid hormones sulfatase inactivation extends lifespan and ameliorates age-related diseases," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20269-y
    DOI: 10.1038/s41467-020-20269-y
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