Increased Skeletal Muscle Mass And Improved Contractile Properties Of Skeletal Muscles Of Old Myostatin-deficient Mice

Abstract

Myostatin (GDF-8) is a negative regulator of muscle mass. The inhibition of myostatin increases both the mass and force generating capacity of skeletal muscles. There is a progressive loss of skeletal muscle mass and force generating capacity that occurs with aging. PURPOSE: We hypothesized that inhibition of myostatin would increase skeletal muscle mass and enhance the contractility of skeletal muscles of old mice. METHODS: To test our hypothesis, we measured the contractile properties of EDL and soleus muscles from 28 to 30 month old male wild type (MSTN+/+), MSTN heterozygous null (MSTN+/-) and MSTN homozygous null (MSTN-/-) mice. RESULTS: Compared with the mass of EDL muscles of MSTN+/+ mice, that of the MSTN+/- mice was 41% greater and that of the MSTN-/- mice 70% greater. Furthermore, compared with the maximum isometric force (Po) of EDL muscles from with MSTN+/+ mice, there was a 48% increase in the Po of MSTN+/- mice and a 29% increase for MSTN-/- mice. For the specific maximum isometric force (sPo) of EDL muscles, no differences were observed. For soleus muscles, the muscle masses of MSTN+/+ mice and MSTN+/- mice were not different, but a 50% greater muscle mass was observed for MSTN-/- mice. Furthermore, compared with the Po of soleus muscles of MSTN+/+ mice, those of MSTN+/- mice showed a 69% increase and those of MSTN-/- mice, a 77% increase. For the soleus muscles of the MSTN-/- mice and the MSTN+/+ mice, no difference was observed for the sPos, but a 70% increase occurred in sPo of MSTN+/- mice. CONCLUSIONS: Our results support a role for the therapeutic inhibition of myostatin in the prevention of the severe muscle atrophy that often occurs with aging.