The ablation of S1P3 receptor protects mouse soleus from age-related drop of muscle mass, force and regenerative capacity.

We investigated the effects of S1P3 deficiency on the age-related atrophy, decline of force and regenerative capacity of soleus muscle from 23-month-old male mice. During ageing, in old wild type mice, soleus mass and muscle fiber cross-sectional area (CSA) were reduced by about 26% and 24%, respectively, compared to the adult muscle. By contrast, the mass and fiber CSA of old S1P3- null soleus were comparable to the adult muscle. Moreover, in wild type soleus twitch and tetanic tensions diminished from adult to old age. A slowing of contractile properties was also observed in old wild type soleus. In S1P3-null soleus neither force nor the contractile properties changed during ageing. We also evaluated the regenerative capacity of old S1P3-null soleus by stimulating muscle regeneration through myotoxic injury. After 10 days of regeneration, the mean fiber CSA of old wild type soleus was significantly smaller (- 28%) compared to that of the adult regenerated muscle. On the contrary, the mean fiber CSA of regenerated old S1P3-null soleus was similar to that of the adult muscle. We conclude that in the absence of S1P3 soleus muscle is protected from the decrease of muscle mass and force as well as the attenuation of regenerative capacity, all typical characteristics of ageing.