ArticleThe Journal of clinical investigation2012
SIRT1 protects against emphysema via FOXO3-mediated reduction of premature senescence in mice.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 208 papers.
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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.
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.
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Who cites it
208 citing papers in PubMed, 347 citations in OpenAlex.
- Molecular Mechanisms and Therapeutic Targeting of the Macrophage Metabolic-Epigenetic Interaction Network in Chronic Obstructive Pulmonary Disease.Cell biochemistry and biophysics · 2026Review
- Review
- Fueling the fire: metabolic dysfunction and senescence as drivers of lung aging and disease.Physiological reviews · 2026Review
- Emerging role of SIRT1 in asthma and COPD from molecular mechanisms to translational therapy.iScience · 2026Review
- Regenerative therapeutics for chronic obstructive pulmonary disease.Pharmacological reviews · 2026Review
- HIV disrupts the lung molecular clock, leading to lung inflammation and features of emphysema.Communications biology · 2026Article
- Emerging Mechanistic Links Between Fucosylation and Senescence in Lung Diseases.Journal of respiratory biology and translational medicine · 2026Article
- Evaluating Cordyceps militaris capsules on post-bronchodilator FEVFrontiers in pharmacology · 2026Article
- PRKN Ser131 phosphorylation promotes cigarette smoke-induced mitophagy impairment and epithelial cell senescence via MKK3/p38 MAPK activation: An in vitro and in vivo study.Tobacco induced diseases · 2026Article
- Heterogeneity of Cellular Senescence, Senotyping, and Targeting by Senolytics and Senomorphics in Lung Diseases.International journal of molecular sciences · 2025Review
- Stellate ganglion irradiation alleviates airway inflammation in asthmatic mice via activating SIRT1 signaling pathway.Scientific reports · 2025Article
- Research advances in polyphenols from Chinese herbal medicine for the prevention and treatment of chronic obstructive pulmonary disease: a review.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- A Review of Telomere Attrition in Cancer and Aging: Current Molecular Insights and Future Therapeutic Approaches.Cancers · 2025Review
- Modulating mitochondria with natural extract compounds: from bench to clinical therapeutic opportunities for COPD.Frontiers in pharmacology · 2025Review
- Impact of Areca Catechu Kombucha on Inflammatory Markers and Gut Microbiota - a Review.Medical archives (Sarajevo, Bosnia and Herzegovina) · 2025Review
- Azithromycin Mitigates Tobacco Smoke-Induced Lung Senescence by Modulating the FOXO3A/CCND1 Signaling Pathway.International journal of chronic obstructive pulmonary disease · 2025Article
- Small airway disease as a key factor in COPD: new perspectives and insights.Frontiers in medicine · 2025Review
- A nutrigeroscience approach: Dietary macronutrients and cellular senescence.Cell metabolism · 2024Review
- CD38 Deficiency Protects Mouse Retinal Ganglion Cells Through Activating the NAD+/Sirt1 Pathway in Ischemia-Reperfusion and Optic Nerve Crush Models.Investigative ophthalmology & visual science · 2024Article
- Dronedarone Attenuates Ang II-Induced Myocardial Hypertrophy Through Regulating SIRT1/FOXO3/PKIA Axis.Korean circulation journal · 2024Article
148 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Chronic obstructive pulmonary disease/emphysema (COPD/emphysema) is characterized by chronic inflammation and premature lung aging. Anti-aging sirtuin 1 (SIRT1), a NAD+-dependent protein/histone deacetylase, is reduced in lungs of patients with COPD. However, the molecular signals underlying the premature aging in lungs, and whether SIRT1 protects against cellular senescence and various pathophysiological alterations in emphysema, remain unknown. Here, we showed increased cellular senescence in lungs of COPD patients. SIRT1 activation by both genetic overexpression and a selective pharmacological activator, SRT1720, attenuated stress-induced premature cellular senescence and protected against emphysema induced by cigarette smoke and elastase in mice. Ablation of Sirt1 in airway epithelium, but not in myeloid cells, aggravated airspace enlargement, impaired lung function, and reduced exercise tolerance. These effects were due to the ability of SIRT1 to deacetylate the FOXO3 transcription factor, since Foxo3 deficiency diminished the protective effect of SRT1720 on cellular senescence and emphysematous changes. Inhibition of lung inflammation by an NF-κB/IKK2 inhibitor did not have any beneficial effect on emphysema. Thus, SIRT1 protects against emphysema through FOXO3-mediated reduction of cellular senescence, independently of inflammation. Activation of SIRT1 may be an attractive therapeutic strategy in COPD/emphysema.
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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.