Figure 4.Metabolome drift in the aged murine brain(A) Metabolic drift or a significant increase in variance-drift with age, averaged (left panel) and by specimen (right panel) across three different brain regions. The drift was calculated as a log of metabolite fold change from old (24 months) to reference adult stage (12 months). To calculate the drift-variance within the adult reference stage group (12 months) one biological sample in that group was used as reference, the others as experimental samples. This is why we can observe only five individuals at 12 months time point. The only outlier was one hippocampus extract in one 24 months old individual. The increase in metabolome deviation from the adult reference stage (12 months) was evaluated using the level of significance: 12 months vs. 18 months for Caudoputamen p = 0.46, for Hippocampus p = 0.02, for Cortex p = 0.06; 18 months vs. 24 months p < 10e-18 across all brain regions (B) Heat map representing the metabolome drift at the metabolite level. Hierarchical clustering was based on the similarity of altered metabolite patterns at three different time points (12, 18 and 24 months, see also Figure S3 for PCA). Discriminating metabolites that represent the readout of the aging process in the brain are shown on the right side (Table S5). Two groups of metabolites whose levels change in opposite directions, either downregulated (upper-right half of the heat map) or upregulated (down-right half of the heat map) in the aged mouse brain can be readily distinguished. MS/MS data matching to facilitate metabolite identification is shown in Figure S5.
