論文 - 詳細
| RRC ID | 76065 |
|---|---|
| 著者 | Statzer C, Meng J, Venz R, Bland M, Robida-Stubbs S, Patel K, Petrovic D, Emsley R, Liu P, Morantte I, Haynes C, Mair WB, Longchamp A, Filipovic MR, Blackwell TK, Ewald CY. |
| タイトル | ATF-4 and hydrogen sulfide signalling mediate longevity in response to inhibition of translation or mTORC1. |
| ジャーナル | Nat Commun |
| Abstract |
Inhibition of the master growth regulator mTORC1 (mechanistic target of rapamycin complex 1) slows ageing across phyla, in part by reducing protein synthesis. Various stresses globally suppress protein synthesis through the integrated stress response (ISR), resulting in preferential translation of the transcription factor ATF-4. Here we show in C. elegans that inhibition of translation or mTORC1 increases ATF-4 expression, and that ATF-4 mediates longevity under these conditions independently of ISR signalling. ATF-4 promotes longevity by activating canonical anti-ageing mechanisms, but also by elevating expression of the transsulfuration enzyme CTH-2 to increase hydrogen sulfide (H2S) production. This H2S boost increases protein persulfidation, a protective modification of redox-reactive cysteines. The ATF-4/CTH-2/H2S pathway also mediates longevity and increased stress resistance from mTORC1 suppression. Increasing H2S levels, or enhancing mechanisms that H2S influences through persulfidation, may represent promising strategies for mobilising therapeutic benefits of the ISR, translation suppression, or mTORC1 inhibition. |
| 巻・号 | 13(1) |
| ページ | 967 |
| 公開日 | 2022-2-18 |
| DOI | 10.1038/s41467-022-28599-9 |
| PII | 10.1038/s41467-022-28599-9 |
| PMID | 35181679 |
| PMC | PMC8857226 |
| MeSH | Activating Transcription Factor 4 / genetics Activating Transcription Factor 4 / metabolism* Animals Animals, Genetically Modified Caenorhabditis elegans Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Hydrogen Sulfide / metabolism* Longevity / genetics* Mechanistic Target of Rapamycin Complex 1 / metabolism* Signal Transduction / genetics |
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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 | 426 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm4397 tm4212 |