|Title||Lipoic acid restores age-associated impairment of brain energy metabolism through the modulation of Akt/JNK signaling and PGC1α transcriptional pathway.|
|Publication Type||Journal Article|
|Year of Publication||2013|
|Authors||Jiang T, Yin F, Yao J, Brinton RD, Cadenas E|
|Date Published||2013 Dec|
|Keywords||Aging, AMP-Activated Protein Kinases, Animals, Brain, Cerebral Cortex, Energy Metabolism, Glucose, JNK Mitogen-Activated Protein Kinases, Male, Mitochondrial Turnover, Neurons, Nuclear Respiratory Factor 1, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Proto-Oncogene Proteins c-akt, Rats, Rats, Inbred F344, Signal Transduction, Sirtuin 1, Thioctic Acid, Transcription Factors, Transcription, Genetic|
This study examines the progress of a hypometabolic state inherent in brain aging with an animal model consisting of Fischer 344 rats of young, middle, and old ages. Dynamic microPET scanning demonstrated a significant decline in brain glucose uptake at old ages, which was associated with a decrease in the expression of insulin-sensitive neuronal glucose transporters GLUT3/4 and of microvascular endothelium GLUT1. Brain aging was associated with an imbalance between the PI3K/Akt pathway of insulin signaling and c-Jun N-terminal kinase (JNK) signaling and a downregulation of the PGC1α-mediated transcriptional pathway of mitochondrial biogenesis that impinged on multiple aspects of energy homeostasis. R-(+)-lipoic acid treatment increased glucose uptake, restored the balance of Akt/JNK signaling, and enhanced mitochondrial bioenergetics and the PGC1α-driven mitochondrial biogenesis. It may be surmised that impairment of a mitochondria-cytosol-nucleus communication is underlying the progression of the age-related hypometabolic state in brain; the effects of lipoic acid are not organelle-limited, but reside on the functional and effective coordination of this communication that results in improved energy metabolism.
|Alternate Journal||Aging Cell|
|PubMed Central ID||PMC3819405|
|Grant List||P01 AG026572 / AG / NIA NIH HHS / United States |
R01 AG016718 / AG / NIA NIH HHS / United States
P01AG026572 / AG / NIA NIH HHS / United States
R01AG016718 / AG / NIA NIH HHS / United States
Lipoic acid restores age-associated impairment of brain energy metabolism through the modulation of Akt/JNK signaling and PGC1α transcriptional pathway.
Faculty Member Reference:
Roberta Diaz Brinton, Ph.D