Age-dependent Effects Of Statin Treatment On Contractile And Myogenic Adaptations To Functional Overload In Mice

Muscle hypertrophy induced by functional overload (FO) provides an in vivo model to study muscle growth. Statin treatment is associated with muscle myopathy and we previously reported statin treatment during treadmill training reduced muscle force vs. placebo. PURPOSE: We hypothesized that statin treatment would impair contractile and myogenic muscle adaptations to a growth stimulus and these effects would be exacerbated with aging. METHODS: Adult and aged (22-24 months) mice underwent FO of the plantaris or sham surgery. In vivo plantaris isometric force and fatigue resistance (% of maximal force after 10 contractions) were measured 14d after FO or sham in mice receiving daily atorvastatin (30 mg/kg body mass (BM)) or placebo (n = 8-10/group). Plantaris basic fibroblast growth factor (bFGF) and insulin-like growth factor 1 (IGF-1) were measured by ELISA. RESULTS: There was a significant main effect of FO on plantaris mass in adult and aged mice independent of statins. FO increased mass in young mice 93 and 58% and in old mice 100 and 67% in placebo and statin, respectively (p < 0.05). There was a significant main effect of statin treatment and interaction on maximal force in young mice. Statin treatment decreased force in FO but not sham mice. Force increased 14% with placebo FO (0.42 ± 0.02 to 0.48 ± 0.02 g/mg BM) but decreased 34% with statin FO (0.44 ± 0.03 to 0.32 ± 0.03 g/mg BM) vs. sham (p < 0.05). In aged mice, there were significant main effects of FO and statins on maximal force with decreases in both groups but greater decreases with statins. FO decreased force from 0.58 ± 0.03 to 0.40 ± 0.04 g/mg BM with placebo and from 0.49 ± 0.05 to 0.30 ± 0.04 g/mg BM with statin vs. sham (p < 0.05). Fatigue resistance was not different among all conditions in young and aged mice. In young mice [IGF-1] and [bFGF] increased with FO in both groups vs. sham with greater increases observed with placebo (p < 0.05). In old mice [IGF-1] increased with FO in both groups vs. sham with greater increases with placebo (p < 0.05). CONCLUSIONS: These data suggest that statin treatment in young and old mice negatively affects contractile and myogenic adaptations to a hypertrophic stimulus, but responses were not exacerbated with aging. Statins attenuated the bFGF and IGF-1 responses to FO in young mice and IGF-1 responses in old mice.