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

Autor:	Hsieh PN; 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., Zhou G; 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., Yuan Y; Department of Pharmacology, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH, 44106, USA., Zhang R; 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., Prosdocimo DA; 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., Sangwung P; 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 Physiology and Biophysics, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH, 44106, USA., Borton AH; 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., Boriushkin E; 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., Hamik A; 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., Fujioka H; Electron Microscopy Facility, 10900 Euclid Avenue, Cleveland, OH, 44106, USA.; Department of Pharmacology, Center for Mitochondrial Diseases, 10900 Euclid Avenue, Cleveland, OH, 44106, USA., Fealy CE; Department of Biomedical Sciences, Kent State University, Cunningham Hall, Kent, OH, 44242, USA., Kirwan JP; 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., Peters M; Department of Biology, Oberlin College, 119 Woodland Street, Oberlin, OH, 44074, USA., Lu Y; 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., Liao X; 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., Ramírez-Bergeron D; 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., Feng Z; Department of Pharmacology, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH, 44106, USA. zxf17@case.edu., Jain MK; Department of Medicine, Case Cardiovascular Research Institute, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH, 44106, USA. mxj84@case.edu.; Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, 2103 Cornell Road, Cleveland, OH, 44106, USA. mxj84@case.edu.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2017 Oct 13; Vol. 8 (1), pp. 914. Date of Electronic Publication: 2017 Oct 13.
DOI:	10.1038/s41467-017-00899-5
Abstrakt:	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.
Databáze:	MEDLINE
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