ArticleAging cell2023
Chronic alcohol metabolism results in DNA repair infidelity and cell cycle-induced senescence in neurons.
Article in Aging cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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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
23 citing papers in PubMed, 32 citations in OpenAlex.
- Therapeutics for Alcohol-Associated Liver Disease.Annual review of pharmacology and toxicology · 2026Review
- AlteredeNeuro · 2026Article
- Ethanol induces neuroimmune dysregulation and soluble TREM2 generation in a human iPSC neuron, astrocyte, microglia triculture model.Alcohol (Fayetteville, N.Y.) · 2026Article
- Association Between Mefox and Prevalence of COPD: Evidence from NHANES 2011-2020.Healthcare (Basel, Switzerland) · 2025Article
- Perimenopausal state oestradiol to progesterone imbalance drives Alzheimer's risk via ERRα dysregulation and energy dyshomeostasis.Nature communications · 2025Article
- AlteredbioRxiv : the preprint server for biology · 2025Article
- Gene expression composite scores of cellular senescence predict aging health outcomes in the Health and Retirement Study.Nature communications · 2025Article
- Recent advances in alcohol metabolism: from the gut to the brain.Physiological reviews · 2025Review
- Senescent brain cell types in Alzheimer's disease: Pathological mechanisms and therapeutic opportunities.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Roles of Oxidative Stress and Autophagy in Alcohol-Mediated Brain Damage.Antioxidants (Basel, Switzerland) · 2025Review
- Alcohol Consumption and Breast and Ovarian Cancer Development: Molecular Pathways and Mechanisms.Current issues in molecular biology · 2024Review
- Associations of three healthy dietary patterns with homeostatic dysregulation: results from the China Multi-Ethnic Cohort study.The journal of nutrition, health & aging · 2024Article
- SenNet recommendations for detecting senescent cells in different tissues.Nature reviews. Molecular cell biology · 2024Review
- Polygenic risk for alcohol use disorder affects cellular responses to ethanol exposure in a human microglial cell model.Science advances · 2024Article
- Nature's Secret Neuro-Regeneration Pathway in Axolotls, Polychaetes and Planarians for Human Therapeutic Target Pathways.International journal of molecular sciences · 2024Review
- Therapeutic targeting of senescent cells in the CNS.Nature reviews. Drug discovery · 2024Review
- The role of cellular senescence in neurodegenerative diseases.Archives of toxicology · 2024Review
- Mitochondrial Aldehyde Dehydrogenase 2 (ALDH2) Protects against Binge Alcohol-Mediated Gut and Brain Injury.Cells · 2024Article
- Upregulated GIRK2 Counteracts Ethanol-Induced Changes in Excitability and Respiration in Human Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Neuronal cell cycle reentry events in the aging brain are more prevalent in neurodegeneration and lead to cellular senescence.PLoS biology · 2024Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 3 countries.
Funding
Abstract
Chronic binge-like drinking is a risk factor for age-related dementia, however, the lasting and irreversible effect of alcohol on the brain remains elusive. Transcriptomic changes in brain cortices revealed pro-ageing hallmarks upon chronic ethanol exposure and these changes predominantly occur in neurons. The changes are attributed to a prioritized ethyl alcohol oxidation in these cells via the NADPH-dependent cytochrome pathway. This hijacks the folate metabolism of the 1-carbon network which supports the pathway choice of DNA repair via the non-cell cycle-dependent mismatch repair networks. The lost-in-function of such results in the de-inactivation of the less preferred cell cycle-dependent homologous recombination (HR) repair, forcing these post-mitotic cells to re-engage in a cell cycle-like process. However, mature neurons are post-mitotic. Therefore, instead of successfully completing a full round of cell cycle which is necessary for the completion of HR-mediated repair; these cells are arrested at checkpoints. The resulting persistence of repair intermediates induces and promotes the nuclear accumulation of p21 and cyclin B-a trigger for permanent cell cycle exits and irreversible senescence response. Supplementation of bioactive 5-methyl tetrahydrofolate simultaneously at times with ethyl alcohol exposure supports the fidelity of the 1-carbon network and hence the activity of the mismatch repair. This prevents aberrant and irreversible cell cycle re-entry and senescence events of neurons. Together, our findings offer a direct connection between binge-drinking behaviour and its irreversible impact on the brain, which makes it a potential risk factor for dementia.
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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 Socratic graph.