3,New SCI Journal Finding: The "Guardian" of Brain Health – AKG
AKG is a central metabolite in the Tricarboxylic Acid (TCA) Cycle, acting like a "key cog" in the cellular energy factory. It not only participates in energy production but also regulates redox balance and the aging process. In recent years, scientists have discovered its significant potential in the anti-aging field.
Recently, a study published in Pharmaceuticals in July 2025 by a team from Sun Yat-sen University revealed the surprising potential of AKG in delaying brain aging. By simulating brain aging in cells and mice, the researchers discovered the following key benefits of AKG:
1)Improves Memory and Learning Ability
In experiments with aging-simulated mice, those supplemented with AKG performed excellently in the "Morris water maze" (a classic learning and memory test). They found the hidden platform faster and remembered its location more frequently, indicating significant improvement in their spatial learning and memory abilities. Their balance and motor coordination were also enhanced. (Figure 1)
2)Potent "Antioxidant," Clears Brain "Rust"
AKG significantly increased the levels of two key antioxidants in the brain and blood: Superoxide Dismutase (SOD) and Glutathione (GSH), effectively equipping the brain with a more powerful "rust remover." Simultaneously, it effectively reduced levels of harmful substances like Malondialdehyde (MDA), a lipid peroxidation product, thereby alleviating oxidative damage at its source. (Figure 2)
3)Repairs the Cellular "Powerhouse" – Mitochondria
The aging brain often suffers from an "energy crisis." AKG can restore mitochondrial membrane potential and increase ATP (the energy currency) production, reinvigorating weakened neuronal cells and restoring their energy. (Figure 3)
4)Flipping the "Aging Switch": Regulating the mTOR Pathway
The most crucial discovery of this research lies in the mechanism by which AKG delays brain aging. Through proteomic analysis, the researchers found that AKG precisely inhibits a key aging-related signaling pathway called mTOR. This pathway acts like a "master aging switch"; when it's overactive, it accelerates cellular senescence. By inhibiting mTOR, AKG not only reduces oxidative stress but also activates autophagy (a self-cleaning and regenerative mechanism), thereby exerting comprehensive neuroprotective effects.
In simple terms, AKG is like a highly skilled "Brain Maintenance Engineer." It acts directly as an antioxidant to clear "rust," repairs the "powerhouses," and, crucially, flips the "master aging switch" at the command center. It works through multiple avenues to collectively combat the brain's aging process.
References
Guan R, Xue Z, et al. (2025). α-Ketoglutarate Attenuates Oxidative Stress-Induced Neuronal Aging via Modulation of the mTOR Pathway. Pharmaceuticals 18, 1080.
The part 3 will introduce measures to delay brain aging.
