Figure 6. Mitochondrial redox homeostasis is not implicated in the processes of age-related muscle fiber atrophy.
(a) Time course of the changes in mouse body weigh (BW) during the 15-week period of daily SC injections of mito-targeted SS31 peptide. Trend lines indicate no changes in BW during the treatment period, BW was monitored weekly. n = 6 mice/group. (b) Transverse sections of AT muscle from 28 mo old control and SS31-treated mice obtained following the 15-week treatment period, and stained with WGA (5 μg/ml, green), to visualize extracellular matrix, and DAPI (1 μg/ml, blue), to mark nuclei. Scale bar, 400μm. (c) Percentage of fibers showing centrally located nuclei in AT muscle of control and SS31-treated old mice (top left panel); total number of muscle fibers in AT muscle of control and SS31-treated old mice (top right panel); mean minimal Feret’s diameter of individual fibers from AT muscle of control and SS31-treated old mice (bottom panel). n = 6 mice/group. (d) Frequency distribution of fiber size of AT muscle from control and SS31-treated old mice. n = 6 mice/group. (e) Representative western blots of the fast (MHC fast) and slow (MHC slow) MHC content in gastrocnemius (GTN, top panel) and AT muscle (bottom panel) of control and SS31-treated old mice. (f) Maximum isometric specific force measured in situ, normalized to total fiber CSA of extensor digitorum longus (EDL) muscle from control and SS31-treated old mice. n = 6 mice/group. (g) In situ measurements of the drop in maximum isometric specific force of EDL muscle during a series of repeated isometric contractions (300ms, at 100Hz, every 5s), expressed as a percentage of the initial force. Lines represent the average response of 6 muscles, data are not significantly different between control and SS31-treated old mice. n = 6 mice/group. (h) Image of a skinned myofiber isolated from an AT muscle of a 28 mo old mouse, attached to a force transducer and high-speed length controller. Scale bar, 400 μm. (i) Ex vivo measurements of maximum fiber specific force normalized to fiber CSA of skinned myofibers isolated from the AT muscle of control and SS31-treated old mice. n = 30 fibers, 6 mice/group. (j) Ex vivo measurements of the time to peak maximum tension of skinned fibers isolated from the AT muscle of control and SS31-treated old mice. n = 30 fibers, 6 mice/group. Data represent mean ± s.e.m.