ArticleNature communications2022
Sirt6 reprograms myofibers to oxidative type through CREB-dependent Sox6 suppression.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 3 of them syntheses that pooled it.
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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
36 citing papers in PubMed, 3 syntheses or guidelines pooled it, 45 citations in OpenAlex.
- Pooled it
- Recent research advances in pain mechanisms in McCune-Albright syndrome thinking about the pain mechanism of FD/MAS.Journal of orthopaedic surgery and research · 2024Pooled it
- PROKR1-CREB-NR4A2 axis for oxidative muscle fiber specification and improvement of metabolic function.Proceedings of the National Academy of Sciences of the United States of America · 2024Pooled it
- The skeletal muscle slow myosin heavy chain regulates mammalian metabolic homeostasis through the NRF2 pathway.Science advances · 2026Article
- Skeletal Muscle HSF1 Alleviates Age-Associated Sarcopenia and Mitochondrial Function Decline via SIRT3-PGC1α Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- HSD17B7 Counters Bone Loss in Estrogen Deficiency via Estrogen Receptor Stabilization and Mediates the Effect of Raloxifene.MedComm · 2026Article
- SIRT6-Mediated Regulation of TFAM: A Central Mechanism Connecting Nuclear and Mitochondrial Transcriptional Processes and Mitophagy.International journal of biological sciences · 2026Article
- Molecular mechanisms underlying Parkinson's disease and role of phytochemicals, α-synuclein, sirtuins, and incretin mimetics in potential therapy.Frontiers in pharmacology · 2026Review
- SIRT6 in Cancer: Mechanistic Insights into Its Dual Roles in Cancer Biology and Implications for Precision Therapeutic Development.Biomolecules · 2025Review
- The Influence of Sirtuin 6 on Chondrocyte Senescence in Osteoarthritis Under Aging: Focusing on Mitochondrial Dysfunction and Oxidative Stress.Antioxidants (Basel, Switzerland) · 2025Review
- Protective effect of exercise on metabolic dysfunction‑associated fatty liver disease: Potential epigenetic mechanisms (Review).International journal of molecular medicine · 2025Review
- Glucocorticoid-Mediated Skeletal Muscle Atrophy: Molecular Mechanisms and Potential Therapeutic Targets.International journal of molecular sciences · 2025Review
- Microgravity accelerates skeletal muscle degeneration: Functional and transcriptomic insights from an ISS muscle lab-on-chip model.Stem cell reports · 2025Article
- The Functions and Regulatory Mechanisms of Histone Modifications in Skeletal Muscle Development and Disease.International journal of molecular sciences · 2025Review
- Vitamin C-Dependent Intergenerational Inheritance of Enhanced Endurance Performance Following Maternal Exercise.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Activation and inhibition of sirtuins: From bench to bedside.Medicinal research reviews · 2025Review
- Single-nucleus transcriptomics reveals subsets of degenerative myonuclei after rotator cuff tear-induced muscle atrophy.Cell proliferation · 2025Article
- Sympathetic innervation induces exosomal miR-125 transfer from osteoarthritic chondrocytes, disrupting subchondral bone homeostasis and aggravating cartilage damage in aging mice.Journal of advanced research · 2025Article
- Cannabidiol reshapes the gut microbiome to promote endurance exercise in mice.Experimental & molecular medicine · 2025Article
- Kdm2a inhibition in skeletal muscle improves metabolic flexibility in obesity.Nature metabolism · 2025Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Expanding the exercise capacity of skeletal muscle is an emerging strategy to combat obesity-related metabolic diseases and this can be achieved by shifting skeletal muscle fibers toward slow-twitch oxidative type. Here, we report that Sirt6, an anti-aging histone deacetylase, is critical in regulating myofiber configuration toward oxidative type and that Sirt6 activator can be an exercise mimetic. Genetic inactivation of Sirt6 in skeletal muscle reduced while its transgenic overexpression increased mitochondrial oxidative capacity and exercise performance in mice. Mechanistically, we show that Sirt6 downregulated Sox6, a key repressor of slow fiber specific gene, by increasing the transcription of CREB. Sirt6 expression is elevated in chronically exercised humans, and mice treated with an activator of Sirt6 showed an increase in exercise endurance as compared to exercise-trained controls. Thus, the current study identifies Sirt6 as a molecular target for reprogramming myofiber composition toward the oxidative type and for improving muscle performance.
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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.