ArticleThe journals of gerontology. Series A, Biological sciences and medical sciences2018
Nrf2 Deficiency Exacerbates Obesity-Induced Oxidative Stress, Neurovascular Dysfunction, Blood-Brain Barrier Disruption, Neuroinflammation, Amyloidogenic Gene Expression, and Cognitive Decline in Mice, Mimicking the Aging Phenotype.
Article in The journals of gerontology. Series A, Biological sciences and medical sciences, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers, 5 of them syntheses that pooled it.
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Who cites it
121 citing papers in PubMed, 5 syntheses or guidelines pooled it, 156 citations in OpenAlex.
- Association between overweight/obesity and oral health in adults aged 55 and older: a systematic review and meta-analysis.GeroScience · 2026Pooled it
- Overweight and obesity significantly increase colorectal cancer risk: a meta-analysis of 66 studies revealing a 25-57% elevation in risk.GeroScience · 2025Pooled it
- Adherence to the Mediterranean diet and its protective effects against colorectal cancer: a meta-analysis of 26 studies with 2,217,404 participants.GeroScience · 2025Pooled it
- Effects of diabetes on microglial physiology: a systematic review of in vitro, preclinical and clinical studies.Journal of neuroinflammation · 2023Pooled it
- Effect of Growth Hormone on Neuropsychological Outcomes and Quality of Life of Patients with Traumatic Brain Injury: A Systematic Review.Journal of neurotrauma · 2021Pooled it
- Protective effect of dapagliflozin against phenytoin-induced cerebellar dysfunction and histological alterations in rats: the role of SIRT1/Nrf2/HO-1 pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Review
- A Age Related Vascular Senescence: Mystery of Blood-brain Barrier Dysfunction in Neurodegeneration.Molecular neurobiology · 2026Review
- Sleeve gastrectomy improves metabolic health, cognition, and Alzheimer's Disease pathology in 3xTG mice.bioRxiv : the preprint server for biology · 2026Article
- Complement 3a Receptor mediates high fat diet induced hypothalamic accumulation of lipid associated microglia to regulate neuroinflammation and obesity.bioRxiv : the preprint server for biology · 2026Article
- NRF2 deficit prevents pathologic Tau seeding and spreading in an induced tauopathy mouse model.Redox biology · 2026Article
- The alteration of brain function in overweight/obese individuals and the neurological benefit of thymoquinone: uncovering molecular mechanisms.Metabolic brain disease · 2026Review
- Endothelial TRIM47 regulates blood-brain barrier integrity and cognition via the KEAP1/NRF2 signalling pathway in mice.Communications biology · 2026Article
- Modulation of the Receptor Tyrosine Kinase TIE2/International journal of molecular sciences · 2026Article
- Conserved differential expression of DDX helicase and CPEB genes in skeletal muscles potentially influences neuromuscular junctions during aging: a computational analysis.Biogerontology · 2026Article
- Resistance exercise alleviates skeletal muscle atrophy through reduction of oxidative stress via Sestrin1 in C57BL/6J mice.Sports medicine and health science · 2026Article
- Fermented Soybean Pulp Alleviates Disease Progression of 5×FAD Model Mice.Molecular neurobiology · 2025Article
- Impacts of systemic milieu on cerebrovascular and brain aging: insights from heterochronic parabiosis, blood exchange, and plasma transfer experiments.GeroScience · 2025Review
- Sex- and age- differences in the expression of critical blood-brain barrier regulators: a physiological context.Biology of sex differences · 2025Article
- Multiple Demographic, Lifestyle, and Biological Factors Associated With Brain Iron Deposition in the Basal Ganglia: A Comprehensive Analysis of 25,980 UK Biobank Participants.Brain and behavior · 2025Article
61 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
Obesity has deleterious effects on cognitive function in the elderly adults. In mice, aging exacerbates obesity-induced oxidative stress, microvascular dysfunction, blood-brain barrier (BBB) disruption, and neuroinflammation, which compromise cognitive health. However, the specific mechanisms through which aging and obesity interact to remain elusive. Previously, we have shown that Nrf2 signaling plays a critical role in microvascular resilience to obesity and that aging is associated with progressive Nrf2 dysfunction, promoting microvascular impairment. To test the hypothesis that Nrf2 deficiency exacerbates cerebromicrovascular dysfunction induced by obesity Nrf2+/+ and Nrf2-/-, mice were fed an adipogenic high-fat diet (HFD). Nrf2 deficiency significantly exacerbated HFD-induced oxidative stress and cellular senescence, impairment of neurovascular coupling responses, BBB disruption, and microglia activation, mimicking the aging phenotype. Obesity in Nrf2-/- mice elicited complex alterations in the amyloidogenic gene expression profile, including upregulation of amyloid precursor protein. Nrf2 deficiency and obesity additively reduced long-term potentiation in the CA1 area of the hippocampus. Collectively, Nrf2 dysfunction exacerbates the deleterious effects of obesity, compromising cerebromicrovascular and brain health by impairing neurovascular coupling mechanisms, BBB integrity and synaptic function and promoting neuroinflammation. These results support a possible role for age-related Nrf2 dysfunction in the pathogenesis of vascular cognitive impairment and Alzheimer's disease.
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Registered trials
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.