dc.contributor.authorIvanisevic, Julijana
dc.contributor.authorStauch, Kelly L.
dc.contributor.authorPetrascheck, Michael
dc.contributor.authorBenton, H. Paul
dc.contributor.authorEpstein, Adrian A.
dc.contributor.authorFang, Mingliang
dc.contributor.authorGorantla, Santhi
dc.contributor.authorTran, Minerva
dc.contributor.authorHoang, Linh
dc.contributor.authorKurczy, Michael E.
dc.contributor.authorBoska, Michael D.
dc.contributor.authorGendelman, Howard E.
dc.contributor.authorFox, Howard S.
dc.contributor.authorSiuzdak, Gary
dc.identifier.citationIvanisevic, 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.en_US
dc.description.abstractBrain 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.en_US
dc.format.extent21 p.en_US
dc.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 crediteden_US
dc.subjectMetabolic driften_US
dc.subjectHealthy brain agingen_US
dc.titleMetabolic drift in the aging brainen_US
dc.typeJournal Article
dc.contributor.schoolSchool of Civil and Environmental Engineeringen_US
dc.description.versionPublished versionen_US

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