28/02/2025
If the body is a city, metabolism is the transportation system that keeps the city running—it is responsible for converting food into energy, transporting, cleaning, and repairing, and holds the key to aging. Once it becomes unbalanced, it acts as a "driving force" of aging, leading to muscle loss, bone density issues, and even the depletion of collagen in the skin...
Want to inject "new power" into your body's metabolism and restore your youthful state? Perhaps you should learn about AKG, known as the "fountain of youth," which is said to reverse aging.
What is AKG? Is its Anti-Aging Effect as Amazing as Claimed? What Are Its Specific Benefits, and How to Supplement It?
AKG, short for Alpha-Ketoglutarate, was discovered in 1937 by British scientists Krebs and others while studying the citric acid cycle (also known as the TCA cycle, the key pathway in the mitochondria responsible for energy metabolism). The TCA cycle is the essential process through which all sugars, fats, and proteins are converted into ATP, and AKG is the "core gear" in this cycle.
At that time, AKG was just an unnoticed metabolic player. However, in 2014, Professor Brian Kennedy from Singapore, known as the "Father of AKG" in anti-aging research, published a study in the prestigious journal Nature that showed giving AKG to nematodes increased their lifespan by 50%[1]! This experiment catapulted AKG into the spotlight as an "anti-aging potential."
AKG Extends Lifespan by About 50% in Nematodes
Besides lifespan extension, further research confirmed AKG’s close connection to aging.
Studies have shown that between the ages of 40-80, human plasma levels of AKG gradually decrease by about 10 times[2], which directly leads to a drastic drop in metabolic efficiency, bone loss, muscle atrophy, and various other aging issues.
As the anti-aging effects of AKG became more apparent and its mechanisms were better understood, AKG's reputation grew—some even claimed it could surpass NMN, the previous anti-aging superstar. David Sinclair, the discoverer of NMN from Harvard Medical School, has repeatedly expressed his optimism about AKG on social media.
The most astonishing and "out-of-the-box" finding comes from a clinical trial conducted by Professor Brian Kennedy's team: 42 participants aged 63 on average, who took AKG for 7 months, had their physiological age reversed by an average of 8.5 years, with some as much as 16 years younger[3]! Additionally, sleep quality and energy levels improved significantly. Since then, AKG has been labeled the "8.5-year age reversal."
Is it Really That Amazing? What Makes AKG Work Its Anti-Aging and Lifespan-Extending "Magic"?
When the transportation system of a city breaks down, it needs to be cleared, maintained, and repaired. Similarly, as we age, our body suffers from blockages (insufficient energy), trash buildup (toxins), and road aging (cell damage) due to aging metabolism problems.
To tackle these issues, AKG has a "metabolism management" mechanism that helps fight aging.
Clearing Blockages: Restarting Mitochondrial Energy Production
As a "fuel" in the TCA cycle, AKG's main job is to improve mitochondrial efficiency and supply continuous "power" for energy metabolism.
In addition to this primary role, AKG also participates in the conversion between malate and oxaloacetate[4], generating more NAD+, which is then transported to the mitochondria to further promote metabolism and delay aging.
Clearing Trash: Regulating MAPK and mTOR Pathways, Activating Autophagy
AKG activates the AMPK pathway, which suppresses the mTOR pathway that controls cell growth and metabolism, initiating autophagy to help clear "garbage" (damaged proteins and organelles) from the body, thus delaying aging[6].
Paving the Roads: Delaying Epigenetic Aging, Resetting the "Aging Clock"
AKG can activate longevity genes like FoxO, DAF-16, and SIRT, and regulate histone methylation levels related to gene binding, effectively "turning back" the body’s "aging clock" at the cellular level[6].
Maintaining Facilities: Anti-Inflammatory and Antioxidant, Enhancing Stem Cell Activity
AKG regulates inflammatory pathways like NF-κB to lower levels of inflammatory factors, reducing the risk of chronic diseases. It also enhances the activity of hematopoietic stem cells and mesenchymal stem cells[6].
Additionally, AKG reacts directly with hydrogen peroxide (H₂O₂), which induces oxidative stress, to neutralize free radicals. It also activates the Nrf2/ARE signaling pathway to boost antioxidants like glutathione (GSH) in cells, improving their resistance to oxidative damage[7].
With AKG's management, cells become more energetic, metabolism becomes more flexible, and the body’s self-repair ability improves. This helps restore youthfulness from the inside out, benefiting multiple organs like bones, skin, and liver:
Improving Bone Health
AKG promotes collagen synthesis, strengthens bones, and significantly reduces the risk of osteoporosis[8]. Studies have shown that AKG improves the vitality of bone marrow mesenchymal stem cells in elderly mice. In human osteoblasts (bone-forming cells), AKG increases the content of "building materials" like Type I collagen, osteopontin, and osteocalcin, promoting bone formation[9].
A clinical study on postmenopausal women with decreased bone mass showed that daily oral intake of 6g of AKG for 6 months led to an average increase of 1.6% in bone density[10].
Skin Rejuvenation and Wrinkle Reduction
In addition to improving bone collagen, AKG also boosts facial collagen. One study found that AKG increases the expression of proteins like involucrin, filaggrin, and serine palmitoyltransferase, which are essential for skin structure and hydration. Therefore, AKG used externally can reduce wrinkles and make skin more hydrated[11].
For instance, a team from Wuhan developed an AKG cream that, after just 56 days of use, reduced facial wrinkles by 23.64%, eliminated crow's feet by 25.42%, and minimized pores to the point where foundation was no longer needed![12]
Enhancing and Repairing Muscle Function
AKG enhances muscle cell energy metabolism, improves skeletal muscle protein synthesis, and delays muscle atrophy due to metabolic aging[13]. For this reason, AKG is often included in sports supplements used by athletes to improve muscle synthesis and reduce muscle breakdown[14].
A study also showed that adding AKG to postoperative nutrition liquids promoted muscle protein synthesis and prevented muscle protein breakdown, speeding up recovery[15].
Strengthening Immunity and Protecting the Gut
AKG is also known as an immune-nutrient factor, as it is a source of glutamine and glutamic acid. Glutamine is the "fuel" for immune cells, and AKG provides glutamine, enhancing the bactericidal capacity of neutrophils and the phagocytic capacity of macrophages, helping the immune system stay active[16].
With AKG boosting the immune system, the gut barrier function is also strengthened, preventing bacterial infections.
Reducing Inflammation and Protecting Brain Cognition
As mentioned earlier, AKG can reduce chronic low-level inflammation, which is beneficial for alleviating neuroinflammation and maintaining brain health. It may even help prevent neurodegenerative diseases like Alzheimer's[3].
Additionally, numerous clinical and animal studies show that AKG has protective effects on fertility (especially ovaries), reduces scar formation, prevents hair loss, and may have anti-cancer properties, among other benefits...
