--- title: "Krebs cycle intermediates regulate DNA and histone methylation:…" description: "Krebs cycle intermediates influence DNA and histone methylation, suggesting a link between metabolism, epigenetics, and aging." url: "https://magellanlongevity.com/study/akg_krebs.md" canonical: "https://magellanlongevity.com/study/akg_krebs.html" html: "https://magellanlongevity.com/study/akg_krebs.html" type: "study" study_key: "akg_krebs" journal: "Ageing Research Reviews" year: 2014 pmid: "24910305" doi: "10.1016/j.arr.2014.05.004" citations: 1 updated: 2026-09-02 author: "Gabriel Radu, DO" author_credentials: "Physiatrist (PM&R). NY medical license 275110. NPI 1376861765." publisher: "Magellan Longevity" content_format: "markdown" --- # Krebs cycle intermediates regulate DNA and histone methylation: epigenetic impact on the aging process [Home](https://magellanlongevity.com/) › [Research map](https://magellanlongevity.com/longevity-research-map.html) › Krebs cycle intermediates regulate DNA and histone… **HTML version:** https://magellanlongevity.com/study/akg_krebs.html · **In the Magellan app:** https://magellanlongevity.com/#/study/akg_krebs ## Citation | Field | Value | | --- | --- | | Journal | Ageing Research Reviews | | Year | 2014 | | PMID | [24910305](https://pubmed.ncbi.nlm.nih.gov/24910305/) | | DOI | [10.1016/j.arr.2014.05.004](https://doi.org/10.1016/j.arr.2014.05.004) | | Study key | akg_krebs | ## Takeaway Krebs cycle intermediates influence DNA and histone methylation, suggesting a link between metabolism, epigenetics, and aging. ## The question How do Krebs cycle intermediates regulate DNA and histone methylation, and what is their epigenetic impact on the aging process? ## Hypothesis Age-related disturbances in Krebs cycle function induce stochastic epigenetic changes in chromatin structures, which promote the aging process. ## Methods This study is a review of existing literature concerning the epigenetic mechanisms by which Krebs cycle intermediates control DNA and histone methylation. ## Results Krebs cycle intermediates can shape the epigenetic landscape of chromatin by regulating DNA and histone methylation. Specifically, 2-oxoglutarate (α-ketoglutarate) is an obligatory substrate for 2-oxoglutarate-dependent dioxygenases (2-OGDO), which include major enzymes for DNA and histone demethylation (TETs and JmjC demethylases). Conversely, succinate and fumarate, also Krebs cycle intermediates, are potent inhibitors of 2-OGDO enzymes. This balance of Krebs cycle reactions can affect the level of DNA and histone methylation and thus control gene expression. ## Conclusion Krebs cycle intermediates regulate DNA and histone methylation through their involvement with 2-oxoglutarate-dependent dioxygenases. Disturbances in Krebs cycle function may lead to epigenetic changes that contribute to the aging process. ## Limitations This is a review article and does not present new experimental data. The proposed link between age-related Krebs cycle disturbances and stochastic epigenetic changes is a hypothesis based on existing evidence. ## Verbatim from the abstract > Krebs cycle intermediates can shape the epigenetic landscape of chromatin by regulating DNA and histone methylation. ## Where this study is used on Magellan This paper is one of the citations behind the evidence grade on the pages below. Grades are assigned from the published research and are independent of affiliate commissions. | Compound or device | Evidence grade | Graded pages | | --- | --- | --- | | Calcium Alpha-Ketoglutarate (Ca-AKG) | — | — | | All-in-One Longevity Formulation | Emerging evidence | [NOVOS Core All-In-One Sachets](https://magellanlongevity.com/p/12.md) | | Methylation & MTHFR Genetic Testing | — | — | ## Reference 1. **Krebs cycle intermediates regulate DNA and histone methylation: epigenetic impact on the aging process** Ageing Research Reviews 2014 · [PMID 24910305](https://pubmed.ncbi.nlm.nih.gov/24910305/) · [DOI 10.1016/j.arr.2014.05.004](https://doi.org/10.1016/j.arr.2014.05.004) > Krebs cycle intermediates can shape the epigenetic landscape of chromatin by regulating DNA and histone methylation. ## Structured data ```json {"@context":"https://schema.org","@graph":[{"@type":"MedicalWebPage","@id":"https://magellanlongevity.com/study/akg_krebs.html#page","url":"https://magellanlongevity.com/study/akg_krebs.html","name":"Krebs cycle intermediates regulate DNA and histone methylation: epigenetic impact on the aging process","description":"Krebs cycle intermediates influence DNA and histone methylation, suggesting a link between metabolism, epigenetics, and aging.","inLanguage":"en","isPartOf":{"@type":"WebSite","name":"Magellan Longevity","url":"https://magellanlongevity.com/"},"author":{"@type":"Person","name":"Gabriel Radu, DO","jobTitle":"Physiatrist (PM&R)","identifier":[{"@type":"PropertyValue","name":"NPI","value":"1376861765"},{"@type":"PropertyValue","name":"NY medical license","value":"275110"}]},"publisher":{"@type":"Organization","name":"Magellan Longevity","url":"https://magellanlongevity.com/"},"encoding":{"@type":"MediaObject","encodingFormat":"text/markdown","contentUrl":"https://magellanlongevity.com/study/akg_krebs.md"},"dateModified":"2026-09-02"},{"@type":"BreadcrumbList","itemListElement":[{"@type":"ListItem","position":1,"name":"Home","item":"https://magellanlongevity.com/"},{"@type":"ListItem","position":2,"name":"Research map","item":"https://magellanlongevity.com/longevity-research-map.html"},{"@type":"ListItem","position":3,"name":"Krebs cycle intermediates regulate DNA and histone…","item":"https://magellanlongevity.com/study/akg_krebs.html"}]},{"@type":"ScholarlyArticle","@id":"https://magellanlongevity.com/study/akg_krebs.html#study","name":"Krebs cycle intermediates regulate DNA and histone methylation: epigenetic impact on the aging process","headline":"Krebs cycle intermediates regulate DNA and histone methylation: epigenetic impact on the aging process","datePublished":"2014","isPartOf":{"@type":"Periodical","name":"Ageing Research Reviews"},"identifier":"PMID:24910305","url":"https://pubmed.ncbi.nlm.nih.gov/24910305/","sameAs":"https://doi.org/10.1016/j.arr.2014.05.004","abstract":"Krebs cycle intermediates influence DNA and histone methylation, suggesting a link between metabolism, epigenetics, and aging."}]} ``` ## Related on Magellan Longevity - [NOVOS Core All-In-One Sachets](https://magellanlongevity.com/p/12.md) — product graded on this and related evidence - [Alpha-Ketoglutarate dietary supplementation to improve health in humans](https://magellanlongevity.com/study/akg_human.md) - [Rejuvant, a potential life-extending compound formulation with alpha-ketoglutarate and…](https://magellanlongevity.com/study/x4.md) - [Longevity research map](https://magellanlongevity.com/longevity-research-map.html) - [Evidence-based longevity supplements](https://magellanlongevity.com/longevity-supplements.md) ## Scope and disclosures Educational information, not medical advice. Nothing here is intended to diagnose, treat, cure, or prevent any disease. Talk to your physician before starting any supplement or device, especially if you are pregnant, nursing, or taking medication. Editorial firewall: evidence grades are assigned from the published research and are independent of any affiliate commission. As an Amazon Associate, Magellan Longevity earns from qualifying purchases. Reviewed for accuracy by a board-certified physician (DO).