2016
DOI: 10.18632/aging.100961
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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 ab… Show more

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Cited by 75 publications
(53 citation statements)
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References 62 publications
(63 reference statements)
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“…; Ivanisevic et al . ). Metabolomics analysis‐based studies have identified compromised cellular energy status with metabolic imbalances suggesting a failure to maintain metabolite homeostasis (Yin et al .…”
Section: Disturbed Energy Homeostasis As a Hallmark Of Cns Disordersmentioning
confidence: 97%
See 1 more Smart Citation
“…; Ivanisevic et al . ). Metabolomics analysis‐based studies have identified compromised cellular energy status with metabolic imbalances suggesting a failure to maintain metabolite homeostasis (Yin et al .…”
Section: Disturbed Energy Homeostasis As a Hallmark Of Cns Disordersmentioning
confidence: 97%
“…These studies have identified increased adenosine monophosphate (AMP), ATP, purine, and pyrimidine levels (Ivanisevic et al . ) with the accumulation of these metabolites as hallmarks of multiple neurodegenerative diseases (Nyhan ; Yin et al . ).…”
Section: Disturbed Energy Homeostasis As a Hallmark Of Cns Disordersmentioning
confidence: 99%
“…The mechanism switching NME4 from phosphotransfer to lipid transfer function may involve OPA1, which undergoes proteolytic cleavage early during mitophagy, possibly weakening its interaction with NME4 (Figure modified that NME4/NDPK-D-dependent mitophagy also participates in this process. Indeed, NME4/NDPK-D is significantly downregulated in the hippocampus of 2-year-old mice, 53 and NME4/NDPK-D is part of a mortality-predicting signature identified in an age 90+ human cohort. 54 Finally, we provided initial evidence that NME4/NDPK-D-supported CL externalization is also important for apoptosis, 45 and the same may apply for inflammatory situations.…”
Section: Nme4/ndpk-d In CL Signalingmentioning
confidence: 99%
“…Conversely, in a study of over 4000 proteins in mice, Walther et al [81] found no effect of age on overall protein abundances. Similarly, aged mouse brains do not show significant changes in protein abundances compared with young mice, yet large differences were seen in metabolomic profiles between the two groups [82]. However, a study of the Twins U.K. cohort found 13 proteins differentially regulated between young and old individuals, 10 of which were replicated in an independent cohort [83].…”
Section: Proteomics and Metabolomics As Ageing Biomarkersmentioning
confidence: 99%
“…Work in Drosophila found significant down-regulation of fatty acid and sugar metabolism with age [69], and a study of metabolite pathway enrichment in dietary restricted flies showed a global decline in amino acid metabolism in response to dietary restriction [35]. Metabolomic profiles in aged mouse brains show significant changes in amino acid and nucleotide metabolism [82], and nucleotide metabolism is significantly altered with age longitudinally in the common marmoset [88]. In addition, energy metabolism and amino acid metabolism are significantly altered in Alzheimer’s patients compared with cognitively normal individuals [94].…”
Section: Metabolic Pathways Associated With Ageingmentioning
confidence: 99%