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On the benefits of the tryptophan metabolite 3-hydroxyanthranilic acid in Caenorhabditis elegans and mouse aging

Author

Listed:
  • Hope Dang

    (Molecular & Cellular Biology, University of Arizona)

  • Raul Castro-Portuguez

    (Molecular & Cellular Biology, University of Arizona)

  • Luis Espejo

    (Molecular & Cellular Biology, University of Arizona)

  • Grant Backer

    (The Jackson Laboratory)

  • Samuel Freitas

    (Molecular & Cellular Biology, University of Arizona)

  • Erica Spence

    (Molecular & Cellular Biology, University of Arizona)

  • Jeremy Meyers

    (Molecular & Cellular Biology, University of Arizona)

  • Karissa Shuck

    (Molecular & Cellular Biology, University of Arizona)

  • Emily A. Gardea

    (Molecular & Cellular Biology, University of Arizona)

  • Leah M. Chang

    (Molecular & Cellular Biology, University of Arizona)

  • Jonah Balsa

    (Molecular & Cellular Biology, University of Arizona)

  • Niall Thorns

    (Molecular & Cellular Biology, University of Arizona)

  • Caroline Corban

    (The Jackson Laboratory)

  • Teresa Liu

    (The Jackson Laboratory)

  • Shannon Bean

    (The Jackson Laboratory)

  • Susan Sheehan

    (The Jackson Laboratory)

  • Ron Korstanje

    (The Jackson Laboratory)

  • George L. Sutphin

    (Molecular & Cellular Biology, University of Arizona)

Abstract

Tryptophan metabolism through the kynurenine pathway influences molecular processes critical to healthy aging including immune signaling, redox homeostasis, and energy production. Aberrant kynurenine metabolism occurs during normal aging and is implicated in many age-associated pathologies including chronic inflammation, atherosclerosis, neurodegeneration, and cancer. We and others previously identified three kynurenine pathway genes—tdo-2, kynu-1, and acsd-1—for which decreasing expression extends lifespan in invertebrates. Here we report that knockdown of haao-1, a fourth gene encoding the enzyme 3-hydroxyanthranilic acid (3HAA) dioxygenase (HAAO), extends lifespan by ~30% and delays age-associated health decline in Caenorhabditis elegans. Lifespan extension is mediated by increased physiological levels of the HAAO substrate 3HAA. 3HAA increases oxidative stress resistance and activates the Nrf2/SKN-1 oxidative stress response. In pilot studies, female Haao knockout mice or aging wild type male mice fed 3HAA supplemented diet were also long-lived. HAAO and 3HAA represent potential therapeutic targets for aging and age-associated disease.

Suggested Citation

  • Hope Dang & Raul Castro-Portuguez & Luis Espejo & Grant Backer & Samuel Freitas & Erica Spence & Jeremy Meyers & Karissa Shuck & Emily A. Gardea & Leah M. Chang & Jonah Balsa & Niall Thorns & Caroline, 2023. "On the benefits of the tryptophan metabolite 3-hydroxyanthranilic acid in Caenorhabditis elegans and mouse aging," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43527-1
    DOI: 10.1038/s41467-023-43527-1
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    References listed on IDEAS

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