Lipoic acid restores age-associated impairment of brain energy metabolism through the modulation of Akt/JNK signaling and PGC1α transcriptional pathway

Tianyi Jiang, Fei Yin, Jia Yao, Roberta D. Brinton, Enrique Cadenas

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1021-1031
Number of pages11
JournalAging Cell
Volume12
Issue number6
DOIs
StatePublished - Dec 2013
Externally publishedYes

Keywords

  • Brain aging
  • C-Jun N-terminal kinase signaling
  • FDG-PET
  • Insulin signaling
  • Lipoic acid
  • Mitochondria
  • Mitochondrial bioenergetics
  • Mitochondrial biogenesis
  • PGC1α
  • Sirt1

ASJC Scopus subject areas

  • Aging
  • Cell Biology

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