A conserved KLF-autophagy pathway modulates nematode lifespan and mammalian age-associated vascular dysfunction.,Nature Communications

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A conserved KLF-autophagy pathway modulates nematode lifespan and mammalian age-associated vascular dysfunction.
Nature Communications ( IF 14.7 ) Pub Date : 2017-10-13 , DOI: 10.1038/s41467-017-00899-5
Paishiun N Hsieh _{1,

2,

3} , Guangjin Zhou _{1,

2} , Yiyuan Yuan ₄ , Rongli Zhang _{1,

2} , Domenick A Prosdocimo _{1,

2} , Panjamaporn Sangwung _{1,

2,

5} , Anna H Borton _{1,

2,

3} , Evgenii Boriushkin _{1,

2} , Anne Hamik _{1,

2} , Hisashi Fujioka _{6,

7} , Ciaran E Fealy ₈ , John P Kirwan _{9,

10} , Maureen Peters ₁₁ , Yuan Lu _{1,

2} , Xudong Liao _{1,

2} , Diana Ramírez-Bergeron _{1,

2} , Zhaoyang Feng ₄ , Mukesh K Jain _{1,

2}

Affiliation

Department of Medicine, Case Cardiovascular Research Institute, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH, 44106, USA.
Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, 2103 Cornell Road, Cleveland, OH, 44106, USA.
Department of Pathology, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH, 44106, USA.
Department of Pharmacology, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH, 44106, USA.
Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH, 44106, USA.
Electron Microscopy Facility, 10900 Euclid Avenue, Cleveland, OH, 44106, USA.
Department of Pharmacology, Center for Mitochondrial Diseases, 10900 Euclid Avenue, Cleveland, OH, 44106, USA.
Department of Biomedical Sciences, Kent State University, Cunningham Hall, Kent, OH, 44242, USA.
Department of Pathobiology, Lerner Research Institute, 9500 Euclid Avenue, Cleveland Clinic, Cleveland, OH, 44195, USA.
Metabolic Translational Research Center, Cleveland Clinic Foundation, 9500 Euclid Avenue/ M83-02, Cleveland, OH, 44195, USA.
Department of Biology, Oberlin College, 119 Woodland Street, Oberlin, OH, 44074, USA.

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.

中文翻译：

保守的KLF自噬途径可调节线虫的寿命和与哺乳动物年龄相关的血管功能障碍。

自噬减少引起的蛋白质损失和细胞器质量控制的丧失是衰老的标志。然而，长寿生物中自噬的生理和分子调控仍未完全了解。在这里，我们显示Kruppel样转录因子家族是秀丽隐杆线虫自噬和健康跨度的重要调节剂，并且还调节哺乳动物血管性年龄相关的表型。Kruppel样的转录因子缺陷家族减弱了机械上不同的长寿线虫模型的自噬和寿命延长。相反，转录因子过表达的Kruppel样家族以自噬依赖性方式延长线虫的寿命。此外，我们显示出哺乳动物血管因子转录因子4的Kruppel样家族在增加自噬和改善衰老小鼠的血管功能方面具有保守作用。在人类血管内皮中，Kruppel样转录因子4家族的表达也随着年龄的增长而减少。因此，类似Kruppel的转录因子家族构成了秀丽隐杆线虫自噬和寿命调节的转录调控点，在鼠的脉管系统中具有保守作用，并可能影响哺乳动物血管衰老.KLF家族转录因子（KLF）调控许多细胞过程，包括增殖，生存和应激反应。在这里，作者将KLF定位为秀丽隐杆线虫自噬和寿命的重要调节剂，

更新日期：2017-10-13

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