Myostatin deletion causes a shift from small to large nerve fibres. Average radial and ischiatic nerve fibres were categorized into small (0–20 μm2), medium (20–60 μm2) and large (>60 μm2). (A) Mstn−/− (light and dark green) mice showed a tendency towards a reduction in the percentage of small nerve fibres and a significant increase in the percentage of large nerve fibres in the radial nerve compared to mstn+/+ (pink and red) (P = 0.07 and P < 0.03, respectively). A significant interaction between genotype and age was apparent for changes in medium-sized nerve fibres (P = 0.05). (B) mstn−/− ischiatic nerves (light and dark green) showed significant increases in the percentage of medium and large nerve fibres, respectively, compared with mstn+/+ nerves (P < 0.001 and P = 0.05, respectively), with a tendency towards a reduction in small nerve fibres (P = 0.06). In 12-month-old animals, significant genotype-independent changes were seen in the percentage of small nerve fibres during aging (P < 0.02). A significant interaction between genotype and age was apparent for changes in small and large nerve fibres (P < 0.001 and P < 0.05, respectively). (C) Average percentage of small, medium and large radial nerve axons from 6-, 12- and 24-month-old mstn−/− mice. The 24-month-old radial nerves (black) harbour significant increases in small nerve fibres and decreases in large nerve fibres. Error bars displayed as mean ± SEM. (D–F) Representative images of the radial nerve from mstn−/− animals at 6- (D), 12- (E) and 24-months of age (F). Scale bar: 20 μm.