Evidence map›Paper›PMID 31655958›Full record

ReviewGeroScience2019

Nrf2 dysfunction and impaired cellular resilience to oxidative stressors in the aged vasculature: from increased cellular senescence to the pathogenesis of age-related vascular diseases.

Zoltan Ungvari, Stefano Tarantini, Ádám Nyúl-Tóth, Tamas Kiss, Andriy Yabluchanskiy, Tamas Csipo, Priya Balasubramanian, Agnes Lipecz, Zoltan Benyo, Anna Csiszar

Open access · greenAbstract readReview
In one paragraph

Review in GeroScience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
96citing papers in PubMed, 2 pooled it
6.3field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

96 citing papers in PubMed, 2 syntheses or guidelines pooled it, 132 citations in OpenAlex.

  1. Pooled it
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  6. Hepatocyte-SpecificAntioxidants (Basel, Switzerland) · 2026
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  12. Microvascular Health as a Key Determinant of Organismal Aging.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
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36 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 2 countries.

Zoltan UngvariVascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging, Oklahoma Center for Geroscience, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. zoltan-ungvari@ouhsc.edu.ORCID http://orcid.org/0000-0002-6035-6039
Stefano TarantiniVascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging, Oklahoma Center for Geroscience, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Ádám Nyúl-TóthVascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging, Oklahoma Center for Geroscience, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Tamas KissVascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging, Oklahoma Center for Geroscience, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Andriy YabluchanskiyVascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging, Oklahoma Center for Geroscience, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Tamas CsipoVascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging, Oklahoma Center for Geroscience, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Priya BalasubramanianVascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging, Oklahoma Center for Geroscience, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Agnes LipeczVascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging, Oklahoma Center for Geroscience, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Zoltan BenyoDoctoral School of Basic and Translational Medicine, Institute of Clinical Experimental Research, Semmelweis University, Budapest, Hungary.
Anna CsiszarVascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging, Oklahoma Center for Geroscience, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Semmelweis University · HUUniversity of Oklahoma Health Sciences Center · USHUN-REN Szegedi Biológiai Kutatóközpont · HUUniversity of Szeged · HU

Funding

Proteomics CoreP20GM103447 · NIGMS · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI Mark L Lang · 2012 to 2026
$60.2M
Visualizing insulin actions on neuronal metabolism and function using fluorescent biosensorsP20GM125528 · NIGMS · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI Veronica Galvan, William Edmund Sonntag · 2019 to 2026
$17.8M
Targeted DNA Methylation and Mitochondrial Heteroplasmy CoreP30AG050911 · NIA · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI William Edmund Sonntag · 2015 to 2026
$13.9M
GEROSCIENCE TRAINING PROGRAM IN OKLAHOMAT32AG052363 · NIA · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI Benjamin Francis Miller, William Edmund Sonntag · 2017 to 2026
$3.6M
Effects of Radiation on Brain Microvasculature and CognitionR01NS056218 · NINDS · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI CSISZAR, ANNA, SONNTAG, WILLIAM EDMUND · 2007 to 2018
$3.6M
NOVEL APPROACHES FOR REGULATION OF IGF-1 LEVELS THROUGHOUT THE LIFESPANR01AG038747 · NIA · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI SONNTAG, WILLIAM EDMUND · 2011 to 2015
$2.4M
Cerebral microhemorrhages and gait dysfunction in agingR01AG055395 · NIA · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI CSISZAR, ANNA · 2017 to 2025
$2.3M
Radiation-induced astrocyte dysfunction and cognitive declineR01NS100782 · NINDS · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI UNGVARI, ZOLTAN ISTVAN · 2018 to 2022
$1.7M
Microvascular mechanisms of neuroinflammation: role of Nrf2R01AG047879 · NIA · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI CSISZAR, ANNA · 2014 to 2018
$1.5M
NIA NIH HHS P30 AG050911NIA NIH HHS R01-AG038747NIA NIH HHS R01 AG047879NIA NIH HHS R01-AG047879NIA NIH HHS R01-AG055395NIA NIH HHS T32 AG052363NIGMS NIH HHS P20 GM103447NIGMS NIH HHS P20 GM125528NINDS NIH HHS R01-NS056218NINDS NIH HHS R01-NS100782
6 · The paper itself

Abstract

Aging is associated with increased oxidative stress in vascular endothelial and smooth muscle cells, which contribute to the development of a wide range of diseases affecting the circulatory system in older adults. There is growing evidence that in addition to increased production of reactive oxygen species (ROS), aging critically impairs pathways determining cellular resilience to oxidative stressors. In young organisms, the evolutionarily conserved nuclear factor-erythroid-2-related factor 2 (Nrf2)-mediated antioxidant response pathway maintains cellular reduction-oxidation homeostasis and promotes a youthful cellular phenotype by regulating the transcription of an array of cytoprotective (antioxidant, pro-survival, anti-inflammatory and macromolecular damage repair) genes. A critical mechanism by which increased ROS production and Nrf2 dysfunction promote vascular aging and exacerbate pathogenesis of age-related vascular diseases is induction of cellular senescence, an evolutionarily conserved cellular stress response mechanism. Senescent cells cease dividing and undergo distinctive phenotypic alterations, contributing to impairment of angiogenic processes, chronic sterile inflammation, remodeling of the extracellular matrix, and barrier dysfunction. Herein, we review mechanisms contributing to dysregulation of Nrf2-driven cytoprotective responses in the aged vasculature and discuss the multifaceted role of Nrf2 dysfunction in the genesis of age-related pathologies affecting the circulatory system, including its role in induction of cellular senescence. Therapeutic strategies that restore Nrf2 signaling and improve vascular resilience in aging are explored to reduce cardiovascular mortality and morbidity in older adults.

Indexed as

Oxidative StressAgedAgingEndothelium, VascularHumansNF-E2-Related Factor 2Signal TransductionVascular DiseasesNFE2L2 protein, humanNF-E2-Related Factor 2AntioxidantAtherosclerosisNrf2 deficiencyNrf2 dysfunctionOxidative stressReactive oxygen speciesSenescenceStress resistanceVascular agingVascular cognitive impairment

Identifiers

PMID31655958
PMCPMC6925097
OpenAlexW2981727881

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.