ArticleProceedings of the National Academy of Sciences of the United States of America2021
Forestalling age-impaired angiogenesis and blood flow by targeting NOX: Interplay of NOX1, IL-6, and SASP in propagating cell senescence.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 34 citations in OpenAlex.
- Angiogenesis in Lung Regeneration and Aging.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Progranulin deficiency induces premature vascular senescence and dysfunction.American journal of physiology. Heart and circulatory physiology · 2026Article
- Shear-Calibrated High-Intensity Interval Training to Promote Endothelial Autophagy and Delay Vascular Senescence: A Biomarker-Guided Approach.International journal of molecular sciences · 2026Review
- Microvascular Health as a Key Determinant of Organismal Aging.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- NADPH oxidases: redox regulation of cell homeostasis and disease.Physiological reviews · 2025Review
- CD4Circulation · 2025Article
- Regulation of cellular senescence in tumor progression and therapeutic targeting: mechanisms and pathways.Molecular cancer · 2025Review
- Mechanisms and Therapeutic Strategies for Myocardial Ischemia-Reperfusion Injury in Diabetic States.ACS pharmacology & translational science · 2024Review
- NADPH oxidase 4-derived hydrogen peroxide counterbalances testosterone-induced endothelial dysfunction and migration.American journal of physiology. Endocrinology and metabolism · 2024Article
- Role of the CCL5 and Its Receptor, CCR5, in the Genesis of Aldosterone-Induced Hypertension, Vascular Dysfunction, and End-Organ Damage.Hypertension (Dallas, Tex. : 1979) · 2024Article
- Vascular Inflammation and Smooth Muscle Contractility: The Role of Nox1-Derived Superoxide and LRRC8 Anion Channels.Hypertension (Dallas, Tex. : 1979) · 2024Review
- Kielin/chordin-like protein deficiency causes cardiac aging in male mice.Journal of molecular medicine (Berlin, Germany) · 2023Article
- Inhibition of IL-6 signaling prevents serum-induced umbilical cord artery dysfunction from patients with severe COVID-19.American journal of physiology. Regulatory, integrative and comparative physiology · 2023Article
- MicroRNAs in the Regulation of NADPH Oxidases in Vascular Diabetic and Ischemic Pathologies: A Case for Alternate Inhibitory Strategies?Antioxidants (Basel, Switzerland) · 2022Review
- NADPH Oxidases in Diastolic Dysfunction and Heart Failure with Preserved Ejection Fraction.Antioxidants (Basel, Switzerland) · 2022Review
- Review
- An Olive Oil Mill Wastewater Extract Improves Chemotherapeutic Activity Against Breast Cancer Cells While Protecting From Cardiotoxicity.Frontiers in cardiovascular medicine · 2022Article
- Redox Dysregulation in Aging and COPD: Role of NOX Enzymes and Implications for Antioxidant Strategies.Antioxidants (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
In an aging population, intense interest has shifted toward prolonging health span. Mounting evidence suggests that cellular reactive species are propagators of cell damage, inflammation, and cellular senescence. Thus, such species have emerged as putative provocateurs and targets for senolysis, and a clearer understanding of their molecular origin and regulation is of paramount importance. In an inquiry into signaling triggered by aging and proxy instigator, hyperglycemia, we show that NADPH Oxidase (NOX) drives cell DNA damage and alters nuclear envelope integrity, inflammation, tissue dysfunction, and cellular senescence in mice and humans with similar causality. Most notably, selective NOX1 inhibition rescues age-impaired blood flow and angiogenesis, vasodilation, and the endothelial cell wound response. Indeed, NOX1i delivery in vivo completely reversed age-impaired hind-limb blood flow and angiogenesis while disrupting a NOX1-IL-6 senescence-associated secretory phenotype (SASP) proinflammatory signaling loop. Relevant to its comorbidity with age, clinical samples from diabetic versus nondiabetic subjects reveal as operant this NOX1-mediated vascular senescence and inflammation in humans. On a mechanistic level, our findings support a previously unidentified role for IL-6 in this feedforward inflammatory loop and peroxisome proliferator-activated receptor gamma (PPARγ) down-regulation as inversely modulating p65-mediated NOX1 transcription. Targeting this previously unidentified NOX1-SASP signaling axis in aging is predicted to be an effective strategy for mitigating senescence in the vasculature and other organ systems.
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