ArticleCell death & disease2023
SIRT6 is a key regulator of mitochondrial function in the brain.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 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.
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Who cites it
56 citing papers in PubMed, 76 citations in OpenAlex.
- Phase 1, Single-Center, Double-Blind, Randomized, Placebo-Controlled Studies of the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Oral Doses of the Sirtuin 6 Activator SP-624 in Healthy Adults.Clinical pharmacology in drug development · 2025Trial
- Conserved Transcriptomic Signatures of Sirt6 Activity: A Cross-Species RNA-seq Meta-analysis.bioRxiv : the preprint server for biology · 2026Article
- SIRT6 enhances the therapeutic potential of extracellular vesicles in mitigating osteoarthritis in rat models.Stem cell research & therapy · 2026Article
- Emerging role of SIRT1 in asthma and COPD from molecular mechanisms to translational therapy.iScience · 2026Review
- Mechanisms by Which Exercise Delays Brain Aging Through Regulation of the Mitochondrial Quality Control System.Biology · 2026Review
- SIRT6 overexpression counteracts chromatin aging in the male murine liver.Nature communications · 2026Article
- Viral Mimicry of Alzheimer's Disease: Innate Sensing of Self-Nucleic Acids as a Driver of Glial Senescence.Journal of molecular neuroscience : MN · 2026Review
- SIRT7 links H3K36ac epigenetic regulation with genome maintenance in the mouse testis.Nature communications · 2026Article
- Role of Sirtuin 6 in the Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease.Current issues in molecular biology · 2026Review
- DHCR24 in cholesterol metabolism and diseases of the nervous system.Lipids in health and disease · 2026Review
- Vav-iCre-Mediated Deletion of TFAM Is Not Recoverable and Is Consistent with Embryonic Lethality.Genes · 2026Article
- Article
- Mechanistic Links Between the Gut Microbiome and Longevity Therapeutics.Biomedicines · 2026Review
- SIRT6 Relieves Acute Lung Injury by Enhancing PGC-1α Expression and Improving Mitochondrial Function.Current molecular medicine · 2026Article
- Novel therapeutic strategies targeting mitochondrial quality control for metabolic dysfunction-associated steatotic liver disease.Frontiers in physiology · 2026Review
- SIRT6-Mediated Regulation of TFAM: A Central Mechanism Connecting Nuclear and Mitochondrial Transcriptional Processes and Mitophagy.International journal of biological sciences · 2026Article
- Sirtuin 6 mitigates thoracic aortic aneurysm progression via maintenance of mitochondria homeostasis in vascular smooth muscle cells.Acta pharmacologica Sinica · 2026Article
- Histone deacetylase SIRT6 regulates tryptophan catabolism and prevents metabolite imbalance associated with neurodegeneration.Nature communications · 2025Article
- Inhibitory Effect of Sirtuin6 on EndMT by Regulating Oxidative Stress and Autophagy in Coxsackievirus B3-Induced Cardiac Endothelial Cells.Immunity, inflammation and disease · 2025Article
- Lactate levels and heart failure: causal insights from Mendelian randomization and multi-cohort integrated analyses.Future science OA · 2025Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The SIRT6 deacetylase has been implicated in DNA repair, telomere maintenance, glucose and lipid metabolism and, importantly, it has critical roles in the brain ranging from its development to neurodegeneration. Here, we combined transcriptomics and metabolomics approaches to characterize the functions of SIRT6 in mouse brains. Our analysis reveals that SIRT6 is a central regulator of mitochondrial activity in the brain. SIRT6 deficiency in the brain leads to mitochondrial deficiency with a global downregulation of mitochondria-related genes and pronounced changes in metabolite content. We suggest that SIRT6 affects mitochondrial functions through its interaction with the transcription factor YY1 that, together, regulate mitochondrial gene expression. Moreover, SIRT6 target genes include SIRT3 and SIRT4, which are significantly downregulated in SIRT6-deficient brains. Our results demonstrate that the lack of SIRT6 leads to decreased mitochondrial gene expression and metabolomic changes of TCA cycle byproducts, including increased ROS production, reduced mitochondrial number, and impaired membrane potential that can be partially rescued by restoring SIRT3 and SIRT4 levels. Importantly, the changes we observed in SIRT6-deficient brains are also occurring in aging human brains and particularly in patients with Alzheimer's, Parkinson's, Huntington's, and Amyotrophic lateral sclerosis disease. Overall, our results suggest that the reduced levels of SIRT6 in the aging brain and neurodegeneration initiate mitochondrial dysfunction by altering gene expression, ROS production, and mitochondrial decay.
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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.