論文 - 詳細
| RRC ID | 88014 |
|---|---|
| 著者 | Nonninger TJ, Mak J, Gerisch B, Ramponi V, Kawamura K, Ripa R, Schilling K, Latza C, Kölschbach J, Serrano M, Antebi A. |
| タイトル | A TFEB-TGFβ axis systemically regulates diapause, stem cell resilience and protects against a senescence-like state. |
| ジャーナル | Nat Aging |
| Abstract |
Diapause is a long-lived state of resilience that allows organisms to outlast adversity. Caenorhabditis elegans can endure months in a fasting-induced adult reproductive diapause (ARD) and, upon refeeding, regenerate and reproduce. Here we find that mutants of ARD master regulator hlh-30/TFEB arrest in a senescence-like state during ARD and refeeding, in which germline stem cells are characterized by DNA damage, nucleolar expansion, cell cycle arrest and mitochondrial dysfunction, alongside dysregulated immune and growth metabolic signatures, elevated senescence-associated β-galactosidase and premature aging at the organismal level. Forward genetic screens reveal a TFEB-TGFβ signaling axis that systemically controls diapause, stem cell longevity and senescence, aligning nutrient supply to proper metabolism and growth signaling. Notably, TFEB's vital role is conserved in mouse embryonic and human cancer diapause. Thus, ARD offers a powerful model to study stem cell longevity and senescence in vivo, directly relevant to mammals. |
| 巻・号 | 5(7) |
| ページ | 1340-1357 |
| 公開日 | 2025-7-1 |
| DOI | 10.1038/s43587-025-00911-4 |
| PII | 10.1038/s43587-025-00911-4 |
| PMID | 40588651 |
| PMC | PMC12270908 |
| MeSH | Animals Basic Helix-Loop-Helix Leucine Zipper Transcription Factors* / genetics Basic Helix-Loop-Helix Leucine Zipper Transcription Factors* / metabolism Basic Helix-Loop-Helix Proteins Caenorhabditis elegans* / genetics Caenorhabditis elegans* / physiology Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Cellular Senescence* / genetics Cellular Senescence* / physiology Diapause* / genetics Diapause* / physiology Fasting Humans Longevity / genetics Mice Signal Transduction Stem Cells* / physiology Transforming Growth Factor beta* / genetics Transforming Growth Factor beta* / 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 | 59 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.5 |
| リソース情報 | |
| 線虫 | tm1978 tm5755 tm1078 tm178 |