ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2013
Impaired SIRT1 nucleocytoplasmic shuttling in the senescent heart during ischemic stress.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 120 citations in OpenAlex.
- Downregulation of Sirt1 as aging change in advanced heart failure.Journal of biomedical science · 2014Trial
- Article
- Cardiovascular ageing: hallmarks, signaling pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Multi-photon, label-free photoacoustic and optical imaging of NADH in brain cells.Light, science & applications · 2025Article
- SIRT1 mediates the inhibitory effect of Dapagliflozin on EndMT by inhibiting the acetylation of endothelium Notch1.Cardiovascular diabetology · 2023Article
- Alterations of SIRT1/SIRT3 subcellular distribution in aging undermine cardiometabolic homeostasis during ischemia and reperfusion.Aging cell · 2023Article
- Therapeutic opportunities for senolysis in cardiovascular disease.The FEBS journal · 2023Review
- Alterations in mitochondrial dynamics with age-related Sirtuin1/Sirtuin3 deficiency impair cardiomyocyte contractility.Aging cell · 2021Article
- Oxidative Stress-Induced Sirtuin1 Downregulation Correlates to HIF-1α, GLUT-1, and VEGF-A Upregulation in Th1 Autoimmune Hashimoto's Thyroiditis.International journal of molecular sciences · 2021Article
- Differential role of SIRT1/MAPK pathway during cerebral ischemia in rats and humans.Scientific reports · 2021Article
- Histone deacetylases in modulating cardiac disease and their clinical translational and therapeutic implications.Experimental biology and medicine (Maywood, N.J.) · 2021Review
- Gestational Diabetes Mellitus-Associated Hyperglycemia Impairs Glucose Transporter 3 Trafficking in Trophoblasts Through the Downregulation of AMP-Activated Protein Kinase.Frontiers in cell and developmental biology · 2021Article
- Pro-oxidant and degenerative effects of haloperidol under inflammatory conditions in rat; the involvement of SIRT1 and NF-κB signaling pathways.Veterinary research forum : an international quarterly journal · 2021Article
- Antiretroviral Drugs Regulate Epigenetic Modification of Cardiac Cells Through Modulation of H3K9 and H3K27 Acetylation.Frontiers in cardiovascular medicine · 2021Article
- SIRT1 is Required for Exercise-Induced Beneficial Effects on Myocardial Ischemia/Reperfusion Injury.Journal of inflammation research · 2021Article
- SIRT1 promotes pulmonary artery endothelial cell proliferation by targeting the Akt signaling pathway.Experimental and therapeutic medicine · 2020Article
- Longevity genes, cardiac ageing, and the pathogenesis of cardiomyopathy: implications for understanding the effects of current and future treatments for heart failure.European heart journal · 2020Article
- SIRT1/SIRT3 Modulates Redox Homeostasis during Ischemia/Reperfusion in the Aging Heart.Antioxidants (Basel, Switzerland) · 2020Review
- The Role of Sirtuins in Kidney Diseases.International journal of molecular sciences · 2020Review
- Mybl2 rejuvenates heart explant-derived cells from aged donors after myocardial infarction.Aging cell · 2020Article
14 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
A "longevity " gene, sirtuin 1 (SIRT1), can attenuate age-dependent induction of left ventricular dysfunction. This study aimed to characterize the role of SIRT1 in the tolerance of aged heart to ischemic insults. Male C57BL/6 young (4-6 mo) and aged (24-26 mo) mice were used to determine the role of SIRT1 in myocardial ischemia/reperfusion (I/R) tolerance. SIRT1 localization was assessed by confocal microscopy. Immunoblotting was used to evaluate SIRT1 expression and translocation. The results demonstrated that SIRT1 is expressed predominantly as a sumoylated form in cardiomyocyte nuclei. Moreover, cardiac overexpression of desumoylase, sentrin-specific protease 2 (SENP2), significantly reduces nuclear sumoylated SIRT1 levels (P<0.05). Interestingly, I/R stress leads to desumoylation and translocation of nuclear SIRT1 into the cytoplasm in aged but not in young hearts. SIRT1 activity in ischemic young hearts was 3.2-fold higher than that seen in ischemic aged hearts, which suggests that aging causes impaired nucleocytoplasmic shuttling and activation of SIRT1 during ischemic stress. The infarct size in aged and Sirt1(+/-) knockout hearts was higher than that observed in young and Sirt1(+/+) WT littermate hearts, respectively (all P<0.05). SIRT1 agonist, SRT1720, reduced myocardial infarction in both aged and Sirt1(+/-) hearts. Therefore, impaired cardiac SIRT1 activity plays a critical role in the observed increase in susceptibility of the aged heart to I/R injury. SIRT1 agonist can restore this aging-related loss of cardioprotection.
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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.