Document Type
Article
Publication Date
12-14-2023
Original Citation
Dang H,
Castro-Portuguez R,
Espejo L,
Backer G,
Freitas S,
Spence E,
Meyers J,
Shuck K,
Gardea E,
Chang L,
Balsa J,
Thorns N,
Corban C,
Liu T,
Bean S,
Sheehan S,
Korstanje R,
Sutphin G.
On the benefits of the tryptophan metabolite 3-hydroxyanthranilic acid in Caenorhabditis elegans and mouse aging. Nat Commun. 2023;14(1):8338.
Keywords
JMG, Animals, Male, Female, Mice, Kynurenine, Tryptophan, Caenorhabditis elegans, 3-Hydroxyanthranilic Acid, Longevity, Mice, Knockout, Caenorhabditis elegans Proteins
JAX Source
Nat Commun. 2023;14(1):8338.
ISSN
2041-1723
PMID
38097593
DOI
https://doi.org/10.1038/s41467-023-43527-1
Grant
This work was supported by NIH P30AG038070 to Gary Churchill and RK, NIH R35GM133588 to G.L.S., P30CA023074 to Joann B. Sweasy, and the State of Arizona Technology and Research Initiative Fund administered by the Arizona Board of Regents. The mouse work was supported by a pilot award to G.L.S. from The Jackson Laboratory Nathan Shock Center for Excellence in Basic Biology of Aging (NIH P30AG038070). G.L.S. was supported as a Jackson Laboratory Scholar in Aging Award.
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.
Comments
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