Fig. 1: Landscape of protein post-translational modifications in the mouse aging brain.
From: Aging and diet alter the protein ubiquitylation landscape in the mouse brain
A Multi-omics approach scheme used to characterize mouse brain aging (3 or 4 vs. 33 months old, N = 5, biological replicates, males, C57BL/6J). Created in BioRender. Ori, A. (2025) https://BioRender.com/2947h3v. B Percentage of significantly affected transcripts, proteins, or PTMs (Adj.P < 0.05 for proteome and transcriptome, Q < 0.05 for PTMs; absolute log2 (FC) > 0.58). C PCA based on ubiquitylated peptide abundances from mouse brains. Ellipses represent 95% confidence intervals. The percentage of variance explained by each principal component is indicated. D Volcano plot for ubiquitin enrichment in mouse brain aging (N = 5, biological replicates, P values from Spectronaut differential abundance analysis). E Gene set enrichment analysis (GSEA) for ubiquitylated peptides affected by aging based on GO cellular component terms (Adj.P < 0.05, weighted Kolmogorov–Smirnov test). F Scatterplot illustrating the relationship between fold changes in protein abundance and corresponding ubiquitylated peptide levels with age. Proteins showing significant age-related changes at both the total protein (Adj. P < 0.05 from limma’s empirical Bayes moderated t-test) and ubiquitylated peptide level (Q < 0.05 from Spectronaut differential abundance analysis) are highlighted in orange. Proteins with significant changes in ubiquitylation only (Adj. P ≥ 0.05; Q < 0.01) are shown in purple. Two-sided Pearson’s correlation test. G, H Examples of proteins showing age-related changes of ubiquitylation (N = 5, biological replicates, Q values from Spectronaut for ubiquitylation and Adj.P from limma’s empirical Bayes moderated t-test for proteome, data shown as averages ± SD). I Correlation between ubiquitylation changes and protein half-life38 (upper panel) or changes in protein half-life39 during mouse brain aging (bottom panel) (Wilcoxon test). Boxplots show the median, 25th and 75th percentiles (box bounds), and whiskers extending to 1.5 times the Interquartile range; outliers not shown. *Q or Adj.P ≤ 0.05; **Q or Adj.P ≤ 0.01, ***Q or Adj.P ≤ 0.001, ****Q or Adj.P ≤ 0.0001. Source data are provided as a Source Data file. Specific P values are listed in Supplementary Data 8. Related to Figs. S1–S4, and Supplementary Data 1 and 2.
