論文 - 詳細
| RRC ID | 80883 |
|---|---|
| 著者 | Dang H, Castro-Portuguez R, Espejo L, Backer G, Freitas S, Spence E, Meyers J, Shuck K, Gardea EA, Chang LM, Balsa J, Thorns N, Corban C, Liu T, Bean S, Sheehan S, Korstanje R, Sutphin GL. |
| タイトル | On the benefits of the tryptophan metabolite 3-hydroxyanthranilic acid in Caenorhabditis elegans and mouse aging. |
| ジャーナル | Nat Commun |
| 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. |
| 巻・号 | 14(1) |
| ページ | 8338 |
| 公開日 | 2023-12-14 |
| DOI | 10.1038/s41467-023-43527-1 |
| PII | 10.1038/s41467-023-43527-1 |
| PMID | 38097593 |
| PMC | PMC10721613 |
| MeSH | 3-Hydroxyanthranilic Acid / metabolism Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Female Kynurenine* / metabolism Longevity / genetics Male Mice Mice, Knockout Tryptophan / metabolism |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 18 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 1.0 |
| リソース情報 | |
| 線虫 | tm4627 tm4924 tm4637 |