Correction: Inhibition of activin A receptor signalling attenuates age-related pathological cardiac remodelling

Phenotypic features of control and Ercc1^Δ/− mice. (A) Body weight was measured for control mice (n=19), Ercc1^Δ/− sActRIIB mice (n=12), Ercc1^Δ/− mice (n=12) and control sActRIIB mice (n=14). Control versus Ercc1^Δ/−, P<0.000001; control versus control sActRIIB, P=0.000123; control versus Ercc1^Δ/− sActRIIB, P<0.000001; Ercc1^Δ/− versus control sActRIIB, P<0.000001; control sActRIIB versus Ercc1^Δ/− sActRIIB, P<0.000001. (B) Heart weight was measured from control mice (n=19), Ercc1^Δ/− sActRIIB mice (n=12), Ercc1^Δ/− mice (n=12) and control sActRIIB mice (n=14). Control versus Ercc1^Δ/−, P<0.000001; control versus control sActRIIB, P=0.035282; control versus Ercc1^Δ/− sActRIIB, P<0.000001; Ercc1^Δ/− versus control sActRIIB, P=0.000006; control sActRIIB versus Ercc1^Δ/− sActRIIB, P=0.000036. (C) Tibia length was measured from control mice (n=11), Ercc1^Δ/− sActRIIB mice (n=6), Ercc1^Δ/− mice (n=7) and control sActRIIB mice (n=4). Control versus Ercc1^Δ/−, P=0.000507; control versus control sActRIIB, P=0.012632; Ercc1^Δ/− versus control sActRIIB, P=0.000003; control sActRIIB versus Ercc1^Δ/− sActRIIB, P<0.000181. (D) Heart weight to tibia length ratio was measured from heart weight and tibia length measurements from control mice (n=11), Ercc1^Δ/− sActRIIB mice (n=6), Ercc1^Δ/− mice (n=7) and control sActRIIB mice (n=4). Control versus Ercc1^Δ/−, P<0.000001; control versus control sActRIIB, P=0.038378; control versus Ercc1^Δ/− sActRIIB, P<0.000001; Ercc1^Δ/− versus control sActRIIB, P=0.000687; control sActRIIB versus Ercc1^Δ/− sActRIIB, P=0.015465. (E-J) Cardiac function of the control and Ercc1^Δ/− mice. (E) Left ventricle (LV) mass was measured from control mice (n=4), Ercc1^Δ/− sActRIIB mice (n=4), Ercc1^Δ/− mice (n=3). Control versus Ercc1^Δ/−, P<0.0001; control versus Ercc1^Δ/− sActRIIB, P<0.0001. (F) Left ventricle internal diameter end of diastole (LVIDd) was measured from control mice (n=4), Ercc1^Δ/− sActRIIB mice (n=4), Ercc1^Δ/− mice (n=3). Control versus Ercc1^Δ/−, P=0.0047; control versus Ercc1^Δ/− sActRIIB, P=0.0003. (G) Interventricular septum thickness in diastole (IVsd) was measured from control mice (n=4), Ercc1^Δ/− sActRIIB mice (n=4), Ercc1^Δ/− mice (n=3). Control versus Ercc1^Δ/−, P=0.0317. One-way ANOVA parametric test was realised followed by a Tukey post-hoc test to compare the mean for different groups. (H) Stroke volume (SV) was measured from control mice (n=4), Ercc1^Δ/− sActRIIB mice (n=4), Ercc1^Δ/− mice (n=3). Control versus Ercc1^Δ/−, P=0.0001; control versus Ercc1^Δ/− sActRIIB, P<0.0001. (I) Cardiac output (CO) was measured from control mice (n=4), Ercc1^Δ/− sActRIIB mice (n=4), Ercc1^Δ/− mice (n=3). Control versus Ercc1^Δ/−, P<0.0001; control versus Ercc1^Δ/− sActRIIB, P<0.0001. (J) Ejection fraction (EF) was measured from control mice (n=4), Ercc1^Δ/− sActRIIB mice (n=4), Ercc1^Δ/− mice (n=3). Control versus Ercc1^Δ/−, P=0.0045; Ercc1^Δ/− sActRIIB versus Ercc1^Δ/− sActRIIB, P=0.0197. (K) Fractional shortening (FS) was measured from control mice (n=4), Ercc1^Δ/− sActRIIB mice (n=4), Ercc1^Δ/− mice (n=3). Control versus Ercc1^Δ/−, P=0.0049; Ercc1^Δ/− sActRIIB versus Ercc1^Δ/− sActRIIB, P=0.0357. All results are expressed as mean±s.d. *P≤0.05, **P<0.01, ***P<0.001. A one-way ANOVA parametric test was followed by a Tukey post-hoc test to compare the mean from different groups.

Phenotypic features of control and Ercc1^Δ/− mice. (A) Body weight was measured for control mice (n=19), Ercc1^Δ/− sActRIIB mice (n=12), Ercc1^Δ/− mice (n=12) and control sActRIIB mice (n=14). Control versus Ercc1^Δ/−, P<0.000001; control versus control sActRIIB, P=0.000123; control versus Ercc1^Δ/− sActRIIB, P<0.000001; Ercc1^Δ/− versus control sActRIIB, P<0.000001; control sActRIIB versus Ercc1^Δ/− sActRIIB, P<0.000001. (B) Heart weight was measured from control mice (n=19), Ercc1^Δ/− sActRIIB mice (n=12), Ercc1^Δ/− mice (n=12) and control sActRIIB mice (n=14). Control versus Ercc1^Δ/−, P<0.000001; control versus control sActRIIB, P=0.035282; control versus Ercc1^Δ/− sActRIIB, P<0.000001; Ercc1^Δ/− versus control sActRIIB, P=0.000006; control sActRIIB versus Ercc1^Δ/− sActRIIB, P=0.000036. (C) Tibia length was measured from control mice (n=11), Ercc1^Δ/− sActRIIB mice (n=6), Ercc1^Δ/− mice (n=7) and control sActRIIB mice (n=4). Control versus Ercc1^Δ/−, P=0.000507; control versus control sActRIIB, P=0.012632; Ercc1^Δ/− versus control sActRIIB, P=0.000003; control sActRIIB versus Ercc1^Δ/− sActRIIB, P<0.000181. (D) Heart weight to tibia length ratio was measured from heart weight and tibia length measurements from control mice (n=11), Ercc1^Δ/− sActRIIB mice (n=6), Ercc1^Δ/− mice (n=7) and control sActRIIB mice (n=4). Control versus Ercc1^Δ/−, P<0.000001; control versus control sActRIIB, P=0.038378; control versus Ercc1^Δ/− sActRIIB, P<0.000001; Ercc1^Δ/− versus control sActRIIB, P=0.000687; control sActRIIB versus Ercc1^Δ/− sActRIIB, P=0.015465. (E-J) Cardiac function of the control and Ercc1^Δ/− mice. (E) Left ventricle (LV) mass was measured from control mice (n=4), Ercc1^Δ/− sActRIIB mice (n=4), Ercc1^Δ/− mice (n=3). Control versus Ercc1^Δ/−, P<0.0001; control versus Ercc1^Δ/− sActRIIB, P<0.0001. (F) Left ventricle internal diameter end of diastole (LVIDd) was measured from control mice (n=4), Ercc1^Δ/− sActRIIB mice (n=4), Ercc1^Δ/− mice (n=3). Control versus Ercc1^Δ/−, P=0.0047; control versus Ercc1^Δ/− sActRIIB, P=0.0003. (G) Interventricular septum thickness in diastole (IVsd) was measured from control mice (n=4), Ercc1^Δ/− sActRIIB mice (n=4), Ercc1^Δ/− mice (n=3). Control versus Ercc1^Δ/−, P=0.0317. One-way ANOVA parametric test was realised followed by a Tukey post-hoc test to compare the mean for different groups. (H) Stroke volume (SV) was measured from control mice (n=4), Ercc1^Δ/− sActRIIB mice (n=4), Ercc1^Δ/− mice (n=3). Control versus Ercc1^Δ/−, P=0.0001; control versus Ercc1^Δ/− sActRIIB, P<0.0001. (I) Cardiac output (CO) was measured from control mice (n=4), Ercc1^Δ/− sActRIIB mice (n=4), Ercc1^Δ/− mice (n=3). Control versus Ercc1^Δ/−, P<0.0001; control versus Ercc1^Δ/− sActRIIB, P<0.0001. (J) Ejection fraction (EF) was measured from control mice (n=4), Ercc1^Δ/− sActRIIB mice (n=4), Ercc1^Δ/− mice (n=3). Control versus Ercc1^Δ/−, P=0.0045; Ercc1^Δ/− sActRIIB versus Ercc1^Δ/− sActRIIB, P=0.0197. (K) Fractional shortening (FS) was measured from control mice (n=4), Ercc1^Δ/− sActRIIB mice (n=4), Ercc1^Δ/− mice (n=3). Control versus Ercc1^Δ/−, P=0.0049; Ercc1^Δ/− sActRIIB versus Ercc1^Δ/− sActRIIB, P=0.0357. All results are expressed as mean±s.d. *P≤0.05, **P<0.01, ***P<0.001. A one-way ANOVA parametric test was followed by a Tukey post-hoc test to compare the mean from different groups.

Gene Ontology (GO) term enrichment analysis from the differentially expressed genes selected with an adjusted P-value<0.05 in the differentially expressed gene sets. Significantly differentially expressed genes were clustered by their gene ontology and the enrichment of gene ontology terms was tested using Fisher exact test (GeneSCF v1.1-p2). (A) Pairwise comparison between control mice and Ercc1^Δ/− mice. (B) Pairwise comparison between untreated Ercc1^Δ/− and treated Ercc1^Δ/− mice. (C) Pairwise comparison between control mice and sActRIIB-treated control mice. (D) Pairwise comparison between sActRIIB-treated control mice and sActRIIB-treated Ercc1^Δ/− mice. n=3 mice were used for each experimental condition.

Gene Ontology (GO) term enrichment analysis from the differentially expressed genes selected with an adjusted P-value<0.05 in the differentially expressed gene sets. Significantly differentially expressed genes were clustered by their gene ontology and the enrichment of gene ontology terms was tested using Fisher exact test (GeneSCF v1.1-p2). (A) Pairwise comparison between control mice and Ercc1^Δ/− mice. (B) Pairwise comparison between untreated Ercc1^Δ/− and treated Ercc1^Δ/− mice. (C) Pairwise comparison between control mice and sActRIIB-treated control mice. (D) Pairwise comparison between sActRIIB-treated control mice and sActRIIB-treated Ercc1^Δ/− mice. n=3 mice were used for each experimental condition.

GO term enrichment analysis from the differentially alternatively spliced genes selected. Genes were selected from the exon sequencing analysis performed by GENEWIZ®. Significantly different alternatively spliced genes were clustered by their gene ontology and the enrichment of gene ontology terms was tested using Fisher exact test with Gene Ontology Resource. P-values were corrected with false discovery rate test. (A) Pairwise comparison between control mice and Ercc1^Δ/− mice. (B) Pairwise comparison between Ercc1^Δ/− mice and sActRIIB-treated Ercc1^Δ/− progeroid mice. (C) Pairwise comparison between control mice and sActRIIB-treated control mice. (D) Pairwise comparison between sActRIIB-treated control mice and sActRIIB-treated Ercc1^Δ/− mice. n=3 mice were used for each experimental condition. (E-H) Venn diagrams highlight the different and overlapping genes between differentially expressed genes (DEG) and differentially alternatively spliced genes (DAS). Pairwise comparison between control mice and Ercc1^Δ/− mice (E). Pairwise comparison between Ercc1^Δ/− mice and sActRIIB-treated Ercc1^Δ/− progeroid mice (F). Pairwise comparison between control mice and sActRIIB-treated control mice (G). Pairwise comparison between sActRIIB-treated control mice and sActRIIB-treated Ercc1^Δ/− mice (H). n=3 mice were used for each experimental condition.

GO term enrichment analysis from the differentially alternatively spliced genes selected. Genes were selected from the exon sequencing analysis performed by GENEWIZ®. Significantly different alternatively spliced genes were clustered by their gene ontology and the enrichment of gene ontology terms was tested using Fisher exact test with Gene Ontology Resource. P-values were corrected with false discovery rate test. (A) Pairwise comparison between control mice and Ercc1^Δ/− mice. (B) Pairwise comparison between Ercc1^Δ/− mice and sActRIIB-treated Ercc1^Δ/− progeroid mice. (C) Pairwise comparison between control mice and sActRIIB-treated control mice. (D) Pairwise comparison between sActRIIB-treated control mice and sActRIIB-treated Ercc1^Δ/− mice. n=3 mice were used for each experimental condition. (E-H) Venn diagrams highlight the different and overlapping genes between differentially expressed genes (DEG) and differentially alternatively spliced genes (DAS). Pairwise comparison between control mice and Ercc1^Δ/− mice (E). Pairwise comparison between Ercc1^Δ/− mice and sActRIIB-treated Ercc1^Δ/− progeroid mice (F). Pairwise comparison between control mice and sActRIIB-treated control mice (G). Pairwise comparison between sActRIIB-treated control mice and sActRIIB-treated Ercc1^Δ/− mice (H). n=3 mice were used for each experimental condition.