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Title: Metabolic drift in the aging brain
Authors: Stauch, Kelly L.
Petrascheck, Michael
Benton, H. Paul
Epstein, Adrian A.
Fang, Mingliang
Gorantla, Santhi
Tran, Minerva
Hoang, Linh
Kurczy, Michael E.
Boska, Michael D.
Gendelman, Howard E.
Fox, Howard S.
Siuzdak, Gary
Ivanisevic, Julijana
Keywords: Metabolic drift
Healthy brain aging
Issue Date: 2016
Source: Ivanisevic, J., Stauch, K. L., Petrascheck, M., Benton, H. P., Epstein, A. A., Fang, M., et al. (2016). Metabolic drift in the aging brain. Aging, 8(5), 1000-1020.
Series/Report no.: Aging
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.
ISSN: 1945-4589
DOI: 10.18632/aging.100961
Rights: © 2016 Ivanisevic et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:CEE Journal Articles

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