Metabolic drift in the aging brain.

Details

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Version: Final published version
Serval ID
serval:BIB_C2AE12DCEAA6
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Metabolic drift in the aging brain.
Journal
Aging
Author(s)
Ivanisevic J., Stauch K.L., Petrascheck M., Benton H.P., Epstein A.A., Fang M., Gorantla S., Tran M., Hoang L., Kurczy M.E., Boska M.D., Gendelman H.E., Fox H.S., Siuzdak G.
ISSN
1945-4589 (Electronic)
ISSN-L
1945-4589
Publication state
Published
Issued date
05/2016
Peer-reviewed
Oui
Volume
8
Number
5
Pages
1000-1020
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Brain function is highly dependent upon controlled energy metabolism whose loss heralds cognitive impairments. This is particularly notable in the aged individuals and in age-related neurodegenerative diseases. However, how metabolic homeostasis is disrupted in the aging brain is still poorly understood. Here we performed global, metabolomic and proteomic analyses across different anatomical regions of mouse brain at different stages of its adult lifespan. Interestingly, while severe proteomic imbalance was absent, global-untargeted metabolomics revealed an energymetabolic drift or significant imbalance in core metabolite levels in aged mouse brains. Metabolic imbalance was characterized by compromised cellular energy status (NAD decline, increased AMP/ATP, purine/pyrimidine accumulation) and significantly altered oxidative phosphorylation and nucleotide biosynthesis and degradation. The central energy metabolic drift suggests a failure of the cellular machinery to restore metabostasis (metabolite homeostasis) in the aged brain and therefore an inability to respond properly to external stimuli, likely driving the alterations in signaling activity and thus in neuronal function and communication.

Keywords
Aging/metabolism, Animals, Brain/metabolism, Energy Metabolism/physiology, Metabolomics, Mice, Oxidative Phosphorylation, Proteomics, energy metabolism, healthy brain aging, metabolic drift, metabolomics, proteomics
Pubmed
Web of science
Create date
06/06/2016 21:40
Last modification date
20/08/2019 16:37
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