Nrf2 deficiency in aged mice exacerbates cellular senescence promoting cerebrovascular inflammation

Gabor A. Fulop, Tamas Kiss, Stefano Tarantini, Priya Balasubramanian, Andriy Yabluchanskiy, E. Farkas, F. Bari, Zoltan Ungvari, Anna Csiszar

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)513-521
Number of pages9
JournalGeroScience
Volume40
Issue number5-6
DOIs
Publication statusPublished - Dec 1 2018

Fingerprint

Cell Aging
Inflammation
Cerebral Arteries
Blood Vessels
Hippocampus
Phenotype
Microglia
Chemokines
Up-Regulation
Pathology
Cytokines

Keywords

  • Endothelial dysfunction
  • Senescence
  • Vascular aging
  • Vascular cognitive impairment
  • VCID

ASJC Scopus subject areas

  • Ageing
  • Geriatrics and Gerontology

Cite this

Fulop, G. A., Kiss, T., Tarantini, S., Balasubramanian, P., Yabluchanskiy, A., Farkas, E., ... Csiszar, A. (2018). Nrf2 deficiency in aged mice exacerbates cellular senescence promoting cerebrovascular inflammation. GeroScience, 40(5-6), 513-521. https://doi.org/10.1007/s11357-018-0047-6

Nrf2 deficiency in aged mice exacerbates cellular senescence promoting cerebrovascular inflammation. / Fulop, Gabor A.; Kiss, Tamas; Tarantini, Stefano; Balasubramanian, Priya; Yabluchanskiy, Andriy; Farkas, E.; Bari, F.; Ungvari, Zoltan; Csiszar, Anna.

In: GeroScience, Vol. 40, No. 5-6, 01.12.2018, p. 513-521.

Research output: Contribution to journalArticle

Fulop, GA, Kiss, T, Tarantini, S, Balasubramanian, P, Yabluchanskiy, A, Farkas, E, Bari, F, Ungvari, Z & Csiszar, A 2018, 'Nrf2 deficiency in aged mice exacerbates cellular senescence promoting cerebrovascular inflammation', GeroScience, vol. 40, no. 5-6, pp. 513-521. https://doi.org/10.1007/s11357-018-0047-6
Fulop, Gabor A. ; Kiss, Tamas ; Tarantini, Stefano ; Balasubramanian, Priya ; Yabluchanskiy, Andriy ; Farkas, E. ; Bari, F. ; Ungvari, Zoltan ; Csiszar, Anna. / Nrf2 deficiency in aged mice exacerbates cellular senescence promoting cerebrovascular inflammation. In: GeroScience. 2018 ; Vol. 40, No. 5-6. pp. 513-521.
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