ArticleOncotarget2016
Aldehyde dehydrogenase 2 activation in aged heart improves the autophagy by reducing the carbonyl modification on SIRT1.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 53 citations in OpenAlex.
- Cardiac ageing: from hallmarks to therapeutic opportunities.Cardiovascular research · 2025Review
- Targeted Overexpression of Mitochondrial ALDH2 in Coronary Endothelial Cells Mitigates HFpEF in a Diabetic Mouse Model.Biomolecules · 2025Article
- Article
- The multifaceted role of autophagy and mitophagy in cardiovascular health and disease.Autophagy reports · 2025Review
- Insights on E1-like enzyme ATG7: functional regulation and relationships with aging-related diseases.Communications biology · 2024Review
- Melatonin enhanced the cardioprotective effects of HTK solution on Langendorff-perfused mouse hearts subjected to ischemia/reperfusion.Iranian journal of basic medical sciences · 2024Article
- Hallmarks of cardiovascular ageing.Nature reviews. Cardiology · 2023Review
- Effects of resveratrol on tolerance to ischemia/reperfusion injury in aged male mice: Role of autophagy and apoptosis.Food science & nutrition · 2023Article
- Puerarin Prevents Cadmium-Induced Neuronal Injury by Alleviating Autophagic Dysfunction in Rat Cerebral Cortical Neurons.International journal of molecular sciences · 2023Article
- The Generation of Nitric Oxide from Aldehyde Dehydrogenase-2: The Role of Dietary Nitrates and Their Implication in Cardiovascular Disease Management.International journal of molecular sciences · 2022Review
- Late-in-life treadmill training rejuvenates autophagy, protein aggregate clearance, and function in mouse hearts.Aging cell · 2021Article
- The role of ALDH2 in tumorigenesis and tumor progression: Targeting ALDH2 as a potential cancer treatment.Acta pharmaceutica Sinica. B · 2021Review
- A role for aldehyde dehydrogenase (ALDH) 2 in angiotensin II-mediated decrease in angiogenesis of coronary endothelial cells.Microvascular research · 2021Article
- FYCO1 Regulates Cardiomyocyte Autophagy and Prevents Heart Failure Due to Pressure Overload In Vivo.JACC. Basic to translational science · 2021Article
- PA28α overexpressing female mice maintain exploratory behavior and capacity to prevent protein aggregation in hippocampus as they age.Aging cell · 2021Article
- Generation and Release of Mitochondrial-Derived Vesicles in Health, Aging and Disease.Journal of clinical medicine · 2020Review
- Endothelial Aldehyde Dehydrogenase 2 as a Target to Maintain Vascular Wellness and Function in Ageing.Biomedicines · 2020Review
- Aldehyde Dehydrogenase 2 Protects Against Post-Cardiac Arrest Myocardial Dysfunction Through a Novel Mechanism of Suppressing Mitochondrial Reactive Oxygen Species Production.Frontiers in pharmacology · 2020Article
- Article
- [Targeted binding of estradiol with ESR1 promotes proliferation of human chondrocytesNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2019Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cardiac aging is characterized by accumulation of damaged proteins and decline of autophagic efficiency. Here, by forestalling SIRT1 carbonylated inactivation in aged heart, we determined the benefits of activation of aldehyde dehydrogenase 2 (ALDH2) on the autophagy. In this study, the ALDH2 KO mice progressively developed age-related heart dysfunction and showed reduction in the life span, which strongly suggests that ALDH2 ablation leads to cardiac aging. What's more, aged hearts displayed a significant decrease ALDH2 activity, resulting in accumulation of 4-HNE-protein adducts and protein carbonyls, impairment in the autophagy flux, and, consequently, deteriorated cardiac function after starvation. Sustained Alda-1 (selective ALDH2 activator) treatment increased cardiac ALDH2 activity and abrogated these effects. Using SIRT1 deficient heterozygous (Sirt1+/-) mice, we found that SIRT1 was necessary for ALDH2 activation-induced autophagy. We further demonstrated that ALDH2 activation attenuated SIRT1 carbonylation and improved SIRT1 activity, thereby increasing the deacetylation of nuclear LC3 and FoxO1. Sequentially, ALDH2 enhanced SIRT1 regulates LC3-Atg7 interaction and FoxO1 increased Rab7 expression, which were both necessary and sufficient for restoring autophagy flux. These results highlight that both accumulation of proteotoxic carbonyl stress linkage with autophagy decline contribute to heart senescence. ALDH2 activation is adequate to improve the autophagy flux by reducing the carbonyl modification on SIRT1, which in turn plays an important role in maintaining cardiac health during aging.
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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.