Figure 1.

Mitochondrial and proteostasis transcript signatures are perturbed in aging and muscle disease

(A) Heatmap analysis of expression datasets from human muscles during aging and a panel of different muscle diseases. The mitochondrial category of gene sets includes sets related to mitochondrial respiration and processes, although proteostasis includes gene sets related to the UPS, amyloid-related processes, and aggregation. See Table S1.

(B and C) Volcano plot representations of an IBM (B; GSE39454, control, n = 5; IBM, n = 10) and a human muscle aging (C; GSE9676, young, n = 14; old, n = 16) dataset, with the mitochondrial and proteostasis gene sets highlighted in green and blue, respectively. See Table S2.

(D) Heatmap of correlations of mitochondrial and proteostasis gene sets with age in the GTEx skeletal muscle expression datasets (male, n = 316; female, n = 175). The datasets used for this analysis are listed in Table S3.

(E) Heatmap analysis of selected gene expression datasets from mouse muscles during aging and selected muscle diseases. The datasets used for this analysis are listed in Table S1.

(F) Module-module association analysis of amyloid-beta formation module (GO:0034205) in human and mouse, using 12 and 11 muscle datasets, respectively (Li et al., 2019). The threshold of significant module-module connection is indicated by the red dashed line. MMAS, module-module association score.