Figure 5.
Functional, morphological, and cellular characterization outcomes in gastrocnemius muscle tissues in TetO-hIL-6mitoQC mice of human IL-6 (hIL-6) induction. (A) Quantification of mouse IL-6 and hIL-6 in gastrocnemius muscle tissue from TetO-hIL-6mitoQC male mice following 6 weeks of hIL-6 induction. N = 4 for uninduced group, N = 5 for induced group. Comparisons were conducted using Student t test. **p < .01. (B) Comparison of in vivo force-frequency curves of gastrocnemius muscle in induced TetO-hIL-6mitoQC male mice at baseline, 3 months postinduction, and 5 months postinduction. N = 5. Data are presented as mean and standard error of the mean (SEM). Comparisons were conducted using 2-way repeated measures ANOVA and Tukey test for post hoc analysis. *p < .05. (C) Collagen type 1 and fibronectin expression in gastrocnemius of uninduced and induced TetO-hIL-6mitoQC mice (following 6 weeks of hIL-6 induction). N = 4 for each group. Data are presented as mean and standard error of the mean (SEM). Comparisons were conducted using Student t test. *p < .05. Representative images of type 1 collagen deposition on gastrocnemius muscle in TetO-hIL-6mitoQC (i) uninduced mice and (ii) induced mice. Representative images of fibronectin deposition on gastrocnemius muscle in TetO-hIL-6mitoQC (iii) uninduced mice and (iv) induced mice. (D) Schematic depicting overall changes in mitochondria and mitophagy at baseline and postinduction (following 6 weeks of hIL-6 induction). From top to bottom, the first graph depicts total mytolysosomes, the second graph shows total intact mitochondria, and the third graph shows the ratio of mitolysosomes to intact mitochondria. *p < .05, **p < .01. Schematic was created with BioRender.com. (E) Protein association network of significantly downregulated genes in gastrocnemius tissue from uninduced and induced TetO-hIL-6mitoQC male mice. N = 4 for each group. Significant fold changes (p < .05) are shown in colored nodes, with their respective fold regulation values depicted as a continuous gradient. Gene network constructed using STRING (v11.5) database via Cytoscape and manually organized to denote aging pathways specific to the RT2 array. Full gene list with fold changes and p values provided in Supplementary File 2.