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Humans have long sought ways to combat aging in the pursuit of longevity. A groundbreaking discovery—α-ketoglutarate is becoming increasingly known as a “longevity molecule.” It is a natural metabolite that not only provides energy for mitochondria but also repairs DNA, clears free radicals, and activates longevity genes such as FOXO and Sirtuins. It has the potential to completely change the way we treat lifespan and vitality.
What is alpha Ketoglutarate？
Alpha ketoglutarate (AKG) is one of the two derivatives of glutaric acid with ketone groups (alpha and beta). Its chemical formula is C5H6O5, which is a white, fine crystalline powder with a melting point of 113.5 °C. It is easily soluble in water and alcohol, but extremely difficult to dissolve in ether.
It is a metabolic product that exists in the human body. In living organisms, alpha-ketoglutarate participates in the tricarboxylic acid cycle and is an intermediate metabolite involved in the synthesis and energy metabolism of amino acids, vitamins, and organic acids. In addition, ketoglutarate also exists as a dietary supplement with broad application prospects, especially in anti-aging and improving health, showing potential value.
What is the tricarboxylic acid cycle？
The tricarboxylic acid cycle (TCA cycle), also known as the citric acid cycle or Krebs cycle, is a critical metabolic pathway in aerobic organisms that primarily releases the energy required by the organism. This cycle occurs within the mitochondria and is the common endpoint for the breakdown of the three major nutrients – sugar, fat, and protein – to provide energy.
In this cycle, acetyl-CoA condenses with oxaloacetate to form citric acid, which undergoes a series of reactions to ultimately produce carbon dioxide and water, and releases energy (ATP). The key enzymes in the tricarboxylic acid cycle include citrate synthase, isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, etc. These enzymes catalyze different steps in the cycle to ensure that the reaction proceeds in an orderly manner.
The tricarboxylic acid cycle helps metabolism, provides energy for cellular processes, helps stimulate collagen synthesis, and also affects age-related processes, including stem cell proliferation. Alpha-Ketoglutarate is not only an important metabolic intermediate in the tricarboxylic acid cycle, but also a biosynthetic precursor for many amino acids, vitamins, and organic acids such as L-glutamate, L-glutamine, L-proline, and L-arginine.
Anti-aging study of alpha Ketoglutarate
In 2014, a research article on AKG was published in the journal Nature, which showed that the TCA cycle intermediate AKG can extend the lifespan of adult Caenorhabditis elegans by about 50%. This also officially opens the way for research on AKG as an anti-aging substance.
In 2019, the journal Aging also published that AKG can prolong the lifespan of fruit flies by inhibiting mTOR and activating AMPK.
In September 2020, two articles published in Cell Metabolism, a subjournal of Cell magazine, proved the research progress of AKG in mammalian mice. The experiment showed that supplementation of calcium a-ketoglutarate (CaAKG) in the diet of middle-aged mice could improve the survival rate of mice, reduce the incidence rate, and reduce frailty, and could inhibit chronic inflammation in female mice and induce T cells to secrete IL-10 (negatively correlated with age).
In 2021, Aging magazine published a retrospective analysis article on the use of AKG supplements (primarily calcium a-ketoglutarate), analyzing the DNA methylation age of 42 individuals (28 males and 14 females, with an average age of approximately 63 years) who took AKG supplements, with an average duration of 7 months. DNA methylation testing was performed at baseline and at the end of supplement therapy. The results showed that the average biological aging of individuals decreased by 8 years.
Alpha-ketoglutarate benefits
1. Maintain mitochondrial function
Alpha-ketoglutarate promotes ATP production and provides sustained energy to cells by optimizing mitochondrial oxidative phosphorylation efficiency. As a bridge for glutamine metabolism, it can alleviate mitochondrial dysfunction and delay energy depletion associated with aging.
2. Activate the longevity signaling pathway
Alpha ketoglutarate activates the longevity protein SIRT family (such as SIRT1/3) and AMPK pathway by increasing intracellular NAD+ levels (converted to glutamate through metabolism and entering the salvage synthesis pathway), enhancing DNA repair ability, and reducing oxidative damage.
3. Clearing free radicals and antioxidant properties
Alpha ketoglutarate directly neutralizes reactive oxygen species (ROS) and enhances the expression of antioxidant enzymes (such as superoxide dismutase (SOD)) by activating the Nrf2 pathway, alleviating the aging phenotype caused by oxidative stress.
4. Inducing autophagy and cell renewal
Alpha ketoglutarate inhibits mTORC1 signaling, activates autophagy, clears senescent cells and damaged organelles (such as dysfunctional mitochondria), maintains cellular homeostasis, and delays tissue degeneration.
5. Stabilize blood sugar and lipid metabolism
Alpha ketoglutarate promotes insulin secretion by pancreatic beta cells and enhances glucose uptake in muscles and liver by activating the AMPK pathway; Simultaneously inhibiting fat synthesis enzymes (such as ACC), promoting fatty acid oxidation, improving obesity and insulin resistance.
6. Cardiovascular protection
By reducing the oxidation of low-density lipoprotein (LDL), inhibiting vascular inflammation (such as NF-κ B pathway), and improving endothelial function, AKG can prevent atherosclerosis and reduce myocardial ischemic injury.
7. Neuroprotective effect
Alpha ketoglutarate, as a precursor of glutamate, supports neurotransmitter synthesis and provides energy through the blood-brain barrier; Its inhibitory effect on neuroinflammation (such as excessive activation of microglia) and reduction of β-amyloid deposition may delay neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease.
8. Bone health
Alpha-ketoglutarate increases bone density and prevents osteoporosis by promoting osteoblast differentiation (activating the Wnt/β – catenin pathway) and inhibiting osteoclast activity (reducing RANKL signaling).
9. Liver detoxification and regeneration
As a substrate of the urea cycle, AKG accelerates the clearance of ammonia and reduces liver damage; Simultaneously, by activating liver cell proliferation signals (such as the HGF/MET pathway), it promotes liver tissue repair.
10. Intestinal barrier repair
Alpha ketoglutarate enhances the expression of tight junction proteins (such as occludin) in intestinal epithelial cells, reduces leaky gut, and alleviates intestinal inflammation by inhibiting the TLR4/NF – κ B pathway, improving diseases such as Crohn’s disease and irritable bowel syndrome (IBS).
11. Regulating immune cell function
Alpha ketoglutarate promotes the anti-inflammatory phenotype of T cells and macrophages (such as M2 macrophages) through metabolic reprogramming, inhibits excessive immune responses, and plays a protective role in autoimmune diseases (such as rheumatoid arthritis) and chronic inflammation.
12. Antitumor adjuvant potential
Alpha ketoglutarate restricts cancer cell proliferation through epigenetic regulation, such as inhibiting histone demethylase KDM4/5; Simultaneously enhancing the anti-tumor activity of T cells, which may be used as adjuvant chemotherapy or immunotherapy
13. Promote collagen synthesis
Alpha ketoglutarate directly supports collagen and elastin production by activating fibroblasts’ proline hydroxylase activity, improving skin wrinkles and sagging.
14. Delaying muscle decay
Inhibiting muscle breakdown (by blocking the ubiquitin proteasome pathway) and promoting protein synthesis (activating mTORC1), AKG can increase muscle mass and strength, and combat muscle atrophy caused by aging or disease.
Conclusion
Alpha Ketoglutarate protects myocardial function and regulates the occurrence and development of cardiovascular diseases such as myocardial infarction, myocardial hypertrophy, and heart failure through antioxidant, anti-inflammatory, and immune system regulation. At the same time, it also plays a positive role in regulating blood pressure, blood lipids, and improving arteriosclerosis.
Due to the easy metabolism of alpha-ketoglutarate in the body, the utilization rate of alpha-ketoglutarate by surrounding tissues is low. Therefore, it is urgent to study how to improve the utilization rate of AKG and the optimal nutritional requirement of AKG in the human body.
Where to buy Alpha-Ketoglutarate?
Runtai Chemical is a professional and reliable Chinese manufacturer of alpha-Ketoglutarate with higher purity and lower price for 15 years. If you are interested in our product, feel free to contact us for free samples!
