Tier 3 — preclinical

α-Ketoglutarate Attenuates Oxidative Stress-Induced Neuronal Aging via Modulation of the mTOR Pathway

Guan R, Xue Z, Huang K, Zhao Y, He G, Dai Y, Liang M, Wen Y, Ye X, Liu P, Chen J
Pharmaceuticals 2025 18(8):1080

Bibliography

PubMed
PMID 40872473
PubMed Central
PMC12388979
DOI
10.3390/ph18081080
Funding
Funded by the Guangdong Basic and Applied Basic Research Foundation (grant 2025A1515011819).
Competing interests
Kaikun Huang and Yanqing Zhao are employees of Shenzhen Xintianhe Biotechnology Co., Ltd. The two authors received support from commercial funding sources associated with companies that sell drugs, medical devices, or medical services. The remaining authors declared no commercial or financial relationships that could be construed as a potential conflict of interest.

Study snapshot

DesignCellular oxidative-stress model plus D-galactose-induced brain-aging mouse study.
ModelHT22 neuronal cells and D-galactose-treated mice.
SampleMultiple cell and mouse cohorts; group sizes varied by experiment.
InterventionAKG exposure in cells and AKG administration in the mouse brain-aging model.
DurationStudy-specific cellular and mouse aging protocols.
EndpointsNeuronal senescence; Cognition; Vestibulomotor function; ROS; Mitochondrial function; mTOR/ULK1 signaling; Autophagy

What the study showed, in plain terms

This 2025 study extends AKG research into oxidative-stress-driven neuronal aging.

AKG reduced senescence markers in neuronal cells and improved cognitive and vestibulomotor deficits in a D-galactose mouse model, with suppression of mTOR and activation of ULK1-linked autophagy.

The paper is preclinical and has relevant commercial affiliations: two authors were employees of Shenzhen Xintianhe Biotechnology and received commercial support.

Key findings

  • AKG reduced oxidative-stress-induced neuronal senescence markers in vitro.
  • AKG improved cognitive and vestibulomotor performance in the mouse aging model.
  • mTOR suppression, ULK1 activation and improved redox/mitochondrial measures accompanied the effects.

What this study can and cannot tell us

  • D-galactose mouse aging model is not normal human brain aging.
  • No oral human Ca-AKG efficacy trial.
  • Two authors had biotechnology-company employment and commercial-support disclosures.

Editorial review

Reviewed by the Biohack Blueprint research team

Last verified

Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology