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A renal clearable fluorogenic probe for in vivo β-galactosidase activity detection during aging and senolysis

Author

Listed:
  • Sara Rojas-Vázquez

    (Universitat Politècnica de València-Universitat de València
    Biomateriales y Nanomedicina (CIBER-BBN)
    Universitat de València)

  • Beatriz Lozano-Torres

    (Universitat Politècnica de València-Universitat de València
    Biomateriales y Nanomedicina (CIBER-BBN)
    Universitat Politècnica de València, Centro de Investigación Príncipe Felipe)

  • Alba García-Fernández

    (Universitat Politècnica de València-Universitat de València
    Biomateriales y Nanomedicina (CIBER-BBN)
    Universitat Politècnica de València, Centro de Investigación Príncipe Felipe)

  • Irene Galiana

    (Universitat Politècnica de València-Universitat de València
    Biomateriales y Nanomedicina (CIBER-BBN)
    Universitat Politècnica de València, Centro de Investigación Príncipe Felipe
    Universitat Politècnica de València, IIS La Fe)

  • Ana Perez-Villalba

    (Universidad Católica de Valencia
    Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED))

  • Pablo Martí-Rodrigo

    (Universitat de València
    Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED))

  • M. José Palop

    (Universitat de València
    Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED))

  • Marcia Domínguez

    (Universitat Politècnica de València-Universitat de València
    Biomateriales y Nanomedicina (CIBER-BBN))

  • Mar Orzáez

    (Universitat Politècnica de València, Centro de Investigación Príncipe Felipe
    Centro de Investigación Príncipe Felipe)

  • Félix Sancenón

    (Universitat Politècnica de València-Universitat de València
    Biomateriales y Nanomedicina (CIBER-BBN)
    Universitat Politècnica de València, Centro de Investigación Príncipe Felipe
    Universitat Politècnica de València, IIS La Fe)

  • Juan F. Blandez

    (Universitat Politècnica de València-Universitat de València
    Biomateriales y Nanomedicina (CIBER-BBN)
    Universitat Politècnica de València, Centro de Investigación Príncipe Felipe
    Universitat Politècnica de València, IIS La Fe)

  • Isabel Fariñas

    (Universitat de València
    Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED))

  • Ramón Martínez-Máñez

    (Universitat Politècnica de València-Universitat de València
    Biomateriales y Nanomedicina (CIBER-BBN)
    Universitat Politècnica de València, Centro de Investigación Príncipe Felipe
    Universitat Politècnica de València, IIS La Fe)

Abstract

Accumulation of senescent cells with age leads to tissue dysfunction and related diseases. Their detection in vivo still constitutes a challenge in aging research. We describe the generation of a fluorogenic probe (sulfonic-Cy7Gal) based on a galactose derivative, to serve as substrate for β-galactosidase, conjugated to a Cy7 fluorophore modified with sulfonic groups to enhance its ability to diffuse. When administered to male or female mice, β-galactosidase cleaves the O-glycosidic bond, releasing the fluorophore that is ultimately excreted by the kidneys and can be measured in urine. The intensity of the recovered fluorophore reliably reflects an experimentally controlled load of cellular senescence and correlates with age-associated anxiety during aging and senolytic treatment. Interestingly, our findings with the probe indicate that the effects of senolysis are temporary if the treatment is discontinued. Our strategy may serve as a basis for developing fluorogenic platforms designed for easy longitudinal monitoring of enzymatic activities in biofluids.

Suggested Citation

  • Sara Rojas-Vázquez & Beatriz Lozano-Torres & Alba García-Fernández & Irene Galiana & Ana Perez-Villalba & Pablo Martí-Rodrigo & M. José Palop & Marcia Domínguez & Mar Orzáez & Félix Sancenón & Juan F., 2024. "A renal clearable fluorogenic probe for in vivo β-galactosidase activity detection during aging and senolysis," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-44903-1
    DOI: 10.1038/s41467-024-44903-1
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    References listed on IDEAS

    as
    1. Lucas von Chamier & Romain F. Laine & Johanna Jukkala & Christoph Spahn & Daniel Krentzel & Elias Nehme & Martina Lerche & Sara Hernández-Pérez & Pieta K. Mattila & Eleni Karinou & Séamus Holden & Ahm, 2021. "Democratising deep learning for microscopy with ZeroCostDL4Mic," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    2. Jan M. van Deursen, 2014. "The role of senescent cells in ageing," Nature, Nature, vol. 509(7501), pages 439-446, May.
    3. Mickey Urdea & Laura A. Penny & Stuart S. Olmsted & Maria Y. Giovanni & Peter Kaspar & Andrew Shepherd & Penny Wilson & Carol A. Dahl & Steven Buchsbaum & Gerry Moeller & Deborah C. Hay Burgess, 2006. "Requirements for high impact diagnostics in the developing world," Nature, Nature, vol. 444(1), pages 73-79, November.
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