Figure 5. Protein Aggregation in Lifespan Mutant Worms During Aging.
(A) Increased aggregate load in daf-2 mutant animals compared to WT, daf-16 and hsf-1 mutant animals at day 12. Relative abundance values of proteins in the insoluble fraction were determined by SILAC quantification. 1367, 1988, 1449 and 1485 proteins were quantified in WT, daf-2, daf-16 and hsf-1 mutant animals, respectively (one representative out of 4 independent experiments is displayed; Table S1F). ****, p-value <2.2 × 10−16 from Wicoxon signed rank test.
(B and C) Quantiled abundance of proteins in the insoluble fraction of daf-2 (352–354 proteins per quantile) (B) and hsf-1 mutant (292 proteins per quantile) (C) relative to WT animals at day 12 plotted against differences in total protein abundance values. Quantile median values are indicated on the X-axis. Proteins that aggregated less in the mutant strains than in the WT have been grouped separately (91 proteins in daf-2 and 259 in hsf-1 mutant).
(D–F) Physico-chemical properties of proteins enriched in the insoluble fractions of daf-2 and hsf-1 mutant relative to WT animals at day 12. (D), Aggregation propensity scores (Z-scores, see Extended Experimental Procedures). ***, p-value <1.4 · 10−4; *, p-value < 0.016, Wilcoxon rank sum test. (E), Net charge. ****, p-value <4.9 · 10−11; (F), Coil content. ***, p-value <1.1 · 10−4. (G), Overall hydrophobicity ****, p-value <2.9 · 10−7. Quantile median values are indicated on both axes and standard errors are reported on the y-axis.