論文 - 詳細
| RRC ID | 51504 |
|---|---|
| 著者 | Hsieh PN, Zhou G, Yuan Y, Zhang R, Prosdocimo DA, Sangwung P, Borton AH, Boriushkin E, Hamik A, Fujioka H, Fealy CE, Kirwan JP, Peters M, Lu Y, Liao X, Ramírez-Bergeron D, Feng Z, Jain MK. |
| タイトル | A conserved KLF-autophagy pathway modulates nematode lifespan and mammalian age-associated vascular dysfunction. |
| ジャーナル | Nat Commun |
| Abstract |
Loss of protein and organelle quality control secondary to reduced autophagy is a hallmark of aging. However, the physiologic and molecular regulation of autophagy in long-lived organisms remains incompletely understood. Here we show that the Kruppel-like family of transcription factors are important regulators of autophagy and healthspan in C. elegans, and also modulate mammalian vascular age-associated phenotypes. Kruppel-like family of transcription factor deficiency attenuates autophagy and lifespan extension across mechanistically distinct longevity nematode models. Conversely, Kruppel-like family of transcription factor overexpression extends nematode lifespan in an autophagy-dependent manner. Furthermore, we show the mammalian vascular factor Kruppel-like family of transcription factor 4 has a conserved role in augmenting autophagy and improving vessel function in aged mice. Kruppel-like family of transcription factor 4 expression also decreases with age in human vascular endothelium. Thus, Kruppel-like family of transcription factors constitute a transcriptional regulatory point for the modulation of autophagy and longevity in C. elegans with conserved effects in the murine vasculature and potential implications for mammalian vascular aging.KLF family transcription factors (KLFs) regulate many cellular processes, including proliferation, survival and stress responses. Here, the authors position KLFs as important regulators of autophagy and lifespan in C. elegans, a role that may extend to the modulation of age-associated vascular phenotypes in mammals. |
| 巻・号 | 8(1) |
| ページ | 914 |
| 公開日 | 2017-10-13 |
| DOI | 10.1038/s41467-017-00899-5 |
| PII | 10.1038/s41467-017-00899-5 |
| PMID | 29030550 |
| PMC | PMC5640649 |
| MeSH | Adult Aged Animals Autophagy* Blood Vessels / physiology Caenorhabditis elegans Caenorhabditis elegans Proteins / metabolism* Cross-Sectional Studies Endothelium, Vascular / metabolism Humans Kruppel-Like Factor 4 Kruppel-Like Transcription Factors / metabolism* Longevity* Male Mice, Inbred C57BL Mice, Transgenic Middle Aged Young Adult |
| IF | 12.121 |
| 引用数 | 19 |
| 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 | 51 |
| 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 | tm731 |