sRAGE accelerates regeneration in aged skeletal muscle after cryoinjury.

A) ELISA measurement of serum sRAGE concentration in 4, 7, 12 and 18 month old C57BL/6J mice (n =  5 male mice per condition). B) Design of AAV9-sRAGE viral vector delivery system comprising of a truncated constitutive CBA hybrid (CBh) promoter, an miRNA-122 target site – to decrease liver targeted expression – alongside the sRAGE transgene, all packaged in a self-complementary backbone. C) Experimental scheme for muscle regeneration assay in vehicle (FBB) and AAV9-sRAGE injected Adult (7–8 months old), and aged (18 months old) mice. D) In vivo kinetics of serum sRAGE levels in vehicle (FBB) and AAV9-sRAGE injected adult mice (n ≥  7 male mice per condition). Enumeration of the mean CSA (E) and distribution (F) of regenerating (centrally nucleated) muscle fibers in vehicle (FBB) and sRAGE treated, adult mice at 7 days after cryoinjury (n ≥  7 male mice per condition). G) In vivo kinetics of serum sRAGE levels in vehicle (FFB) and AAV9-sRAGE injected aged mice (n =  10 male mice per condition). H & I) Enumeration of the mean CSA (H) and distribution (I) of regenerating (centrally nucleated) muscle fibers in vehicle (FFB) and sRAGE treated, aged mice at 7 days post cryoinjury (n =  10 male mice per condition). Quantification of body weight (J), grid hang time (K), exercise endurance (L), and serum glucose levels (M) in vehicle (FFB) and sRAGE treated, aged (18 months old) mice. (n =  10 male mice per condition). Dots represent data for individual animals overlaid with mean ±  SD. Data analyzed for statistical significance by one-way ANOVA with Tukey post hoc test (A, D, G) or Student’s two-tailed unpaired t test (E, H, J, K, L, M). Myofiber size distributions analyzed by Mann-Whitney U test (F, I).