EFFECTS OF AGING AND VOLUNTARY EXERCISE ON THE FUNCTION OF DYSTROPHICMUSCLE FROM MDX MICE

To understand how exercise affects the contractile function of dystrop hic muscle, we examined the effect of long-term voluntary exercise on mdx mice and related these effects to our findings in sedentary aging mice. Although the mdx mouse is the genetic homolog for Duchenne muscu lar dystrophy, it does not demonstrate the same progression in limb mu scle dysfunction as Duchenne muscular dystrophy as it ages. We postula ted that the sedentary lifestyle of this animal plays an important rol e in its minimal phenotypic expression. To examine the effect of exerc ise, eight C57BL/10 (C57) and eight mdx mice were allowed to run ad li bitum for one year. Forty sedentary mdx mice and 40 sedentary C57 from one month to 18 months of age were used as controls. Contractile char acteristics of the extensor digitorum longus and soleus muscles and mo rphometric characteristics of the mice were examined. The mdx mice ran approximately 45% fewer kilometers per day than C57 mice. Long-term v oluntary running had beneficial training effects on both the old mdx m ice and their C57 controls. The exercise ameliorated the age-associate d loss in tension production that was observed in the soleus of sedent ary mdx and sedentary C57 mice. There was a 9% reduction in the fatiga bility of the extensor digitorum longus muscle of the old mdx mice aft er the exercise. Despite these improvements, the old mdx mice exhibite d significant functional deficits compared with their C57 controls. Ou r hypothesis, that long-term voluntary exercise would have a beneficia l training effect on control mice and a deleterious effect on mdx mice as they aged, was not supported by this study. This study shows that dystrophin-less muscles from sedentary mice display significant signs of muscle damage, yet can respond beneficially to low-level voluntary running in a manner similar to that of the C57 control.