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Nrf2 deficiency in aged mice exacerbates cellular senescence promoting cerebrovascular inflammation.
Fulop, Gabor A; Kiss, Tamas; Tarantini, Stefano; Balasubramanian, Priya; Yabluchanskiy, Andriy; Farkas, Eszter; Bari, Ferenc; Ungvari, Zoltan; Csiszar, Anna.
Afiliação
  • Fulop GA; Vascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
  • Kiss T; Translational Geroscience Laboratory, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
  • Tarantini S; Division of Clinical Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
  • Balasubramanian P; Vascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
  • Yabluchanskiy A; Translational Geroscience Laboratory, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
  • Farkas E; Department of Medical Physics and Informatics, University of Szeged, Szeged, Hungary.
  • Bari F; Vascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
  • Ungvari Z; Translational Geroscience Laboratory, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
  • Csiszar A; Vascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Geroscience ; 40(5-6): 513-521, 2018 12.
Article em En | MEDLINE | ID: mdl-30470983
ABSTRACT
Aging-induced pro-inflammatory phenotypic alterations of the cerebral vasculature critically contribute to the pathogenesis of vascular cognitive impairment. Cellular senescence is a fundamental aging process that promotes inflammation; however, its role in cerebrovascular aging remains unexplored. The present study was undertaken to test the hypothesis that advanced aging promotes cellular senescence in the cerebral vasculature. We found that in cerebral arteries of 24-month-old mice, expression of molecular markers of senescence (p16INK4a, p21) is upregulated as compared to that in young controls. Induction of senescence programs in cerebral arteries is associated by an upregulation of a wide range of inflammatory cytokines and chemokines, which are known to contribute to the senescence-associated secretory phenotype (SASP) in vascular cells. Age-related cerebrovascular senescence and inflammation are associated with neuroinflammation, as shown by the molecular footprint of microglia activation in the hippocampus. Genetic depletion of the pro-survival/anti-aging transcriptional regulator Nrf2 exacerbated age-related induction of senescence markers and inflammatory SASP factors and resulted in a heightened inflammatory status of the hippocampus. In conclusion, our studies provide evidence that aging and Nrf2 dysfunction promote cellular senescence in cerebral vessels, which may potentially cause or exacerbate age-related pathology.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Envelhecimento / Transtornos Cerebrovasculares / Senescência Celular / Fator 2 Relacionado a NF-E2 / Disfunção Cognitiva Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Geroscience Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Envelhecimento / Transtornos Cerebrovasculares / Senescência Celular / Fator 2 Relacionado a NF-E2 / Disfunção Cognitiva Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Geroscience Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos