Fig. 5: Impact of dietary intervention on the brain proteome and ubiquitylome of old mice.
From: Aging and diet alter the protein ubiquitylation landscape in the mouse brain
A Scheme of dietary intervention applied to old mice (N = 4 for ad libitum fed mice, N = 6 for re-fed mice, biological replicates, males, C57BL/6J, 26 months old, data shown as averages ± SD). Created in BioRender. Ori, A. (2025) https://BioRender.com/2947h3v. B PCA based on proteome and ubiquitylome data from ad libitum (AL) and re-fed mice (RF). Ellipses represent 95% confidence intervals. The percentage of variance explained by each principal component is indicated. C Percentage of significantly affected proteins, or ubiquitylated peptides (Q < 0.05; absolute log2 fold change (FC) > 0.58). D Volcano plot for protein abundance and ubiquitylated peptide changes in RF vs. AL mice (N = 4 for AL mice, N = 6 for RF mice, biological replicates). E Venn diagram displaying overlap between ubiquitylation significantly (Q < 0.05) affected by aging and dietary intervention (508 sites not significant in both datasets are not displayed, Hypergeometric test). F Scatterplot illustrating the relationship between ubiquitylated peptide changes observed with aging and those following dietary intervention in old mice. Only peptides with significant changes (Q < 0.05) in at least one dataset are shown. Peptides with congruent and significant changes in both datasets (Q < 0.05) are labeled as “Exacerbated” (dark gray). “Reverted-down” (yellow) denotes peptides that significantly decreased upon dietary intervention (Q < 0.05 in RF data) in the opposite direction to the age-related increase. “Reverted-up” (purple) indicates peptides that significantly increased upon intervention in the opposite direction to the age-related decrease. Peptides with consistent directional changes but significant in only one dataset are shown in light gray. Two-sided Pearson’s correlation test. G Heatmap comparing the normalized enrichment scores (NES) from gene set enrichment analyses (GSEA) performed on age-related and diet-induced changes of ubiquitylation. GO terms are sorted by their scaled similarity (1/Euclidean distance between NES), multiplied by the average −log10 (Adj.P) across the two datasets, weighted Kolmogorov–Smirnov test. H Heatmap highlighting age-related changes in ubiquitylation that are reverted by dietary intervention (Q < 0.05 in response to dietary intervention and of opposite log2 (FC) in response to aging). Source data are provided as a Source Data file. Related to Fig. S9 and Supplementary Data 7.
