Metabolic drift in the aging brain

Julijana Ivanisevic, Kelly L. Stauch, Michael Petrascheck, H. Paul Benton, Adrian A. Epstein, Mingliang Fang, Santhi Gorantla, Minerva Tran, Linh Hoang, Michael E. Kurczy, Michael D. Boska, Howard Eliot Gendelman, Howard S Fox, Gary Siuzdak

Research output: Contribution to journalArticle

19 Citations (Scopus)

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 energy metabolic 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.

Original languageEnglish (US)
Pages (from-to)1000-1020
Number of pages21
JournalAging
Volume8
Issue number5
DOIs
StatePublished - Jan 1 2016

Fingerprint

Brain
Metabolomics
Proteomics
Homeostasis
Oxidative Phosphorylation
Adenosine Monophosphate
Neurodegenerative Diseases
NAD
Energy Metabolism
Nucleotides
Adenosine Triphosphate
Communication
Cognitive Dysfunction
pyrimidine
purine

Keywords

  • Energy metabolism
  • Healthy brain aging
  • Metabolic drift
  • Metabolomics
  • Proteomics

ASJC Scopus subject areas

  • Aging
  • Cell Biology

Cite this

Ivanisevic, J., Stauch, K. L., Petrascheck, M., Benton, H. P., Epstein, A. A., Fang, M., ... Siuzdak, G. (2016). Metabolic drift in the aging brain. Aging, 8(5), 1000-1020. https://doi.org/10.18632/aging.100961

Metabolic drift in the aging brain. / Ivanisevic, Julijana; 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 Eliot; Fox, Howard S; Siuzdak, Gary.

In: Aging, Vol. 8, No. 5, 01.01.2016, p. 1000-1020.

Research output: Contribution to journalArticle

Ivanisevic, J, Stauch, KL, Petrascheck, M, Benton, HP, Epstein, AA, Fang, M, Gorantla, S, Tran, M, Hoang, L, Kurczy, ME, Boska, MD, Gendelman, HE, Fox, HS & Siuzdak, G 2016, 'Metabolic drift in the aging brain', Aging, vol. 8, no. 5, pp. 1000-1020. https://doi.org/10.18632/aging.100961
Ivanisevic J, Stauch KL, Petrascheck M, Benton HP, Epstein AA, Fang M et al. Metabolic drift in the aging brain. Aging. 2016 Jan 1;8(5):1000-1020. https://doi.org/10.18632/aging.100961
Ivanisevic, Julijana ; 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 Eliot ; Fox, Howard S ; Siuzdak, Gary. / Metabolic drift in the aging brain. In: Aging. 2016 ; Vol. 8, No. 5. pp. 1000-1020.
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