Open AccessLipoic acid restores age‐associated impairment of brain energy metabolism through the modulation of A kt/ JNK signaling and PGC 1α transcriptional pathway
Author(s) -
Jiang Tianyi,
Yin Fei,
Yao Jia,
Brinton Roberta D.,
Cadenas Enrique
Publication year - 2013
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12127
Subject(s) - biology , metabolism , lipoic acid , energy metabolism , signal transduction , microbiology and biotechnology , biochemistry , endocrinology , antioxidant
Summary 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 micro PET 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 GLUT 3/4 and of microvascular endothelium GLUT 1. Brain aging was associated with an imbalance between the PI 3K/Akt pathway of insulin signaling and c‐Jun N‐terminal kinase ( JNK ) signaling and a downregulation of the PGC 1α‐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 A kt/ JNK signaling, and enhanced mitochondrial bioenergetics and the PGC 1α‐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.