|In the present investigation we compare the expression, basal activation and the ability of muscle stretch to activate the p70S6k pathway in the fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus of adult (6 mo. old), aged (30 mo. old) and very aged (36 mo. old) Fischer 344 x Brown Norway rats. Immunoblotting demonstrated that the tissue content of mTOR, p70S6k, 4E-BP1 and GSK-3â decreased in the EDL and soleus in aged rats, while SHP-2 increased in the EDL and decreased in the soleus when compared to adult rats. Basal phosphorylation of 4E-BP1 increased in both the muscles; however, basal phosphorylation of mTOR increased in EDL while it was decreased in the very aged soleus. Conversely, the basal phosphorylation of GSK-3â and SHP-2 decreased in both the muscles in aged rats. Twenty percent stretch of the EDL muscle increased phosphorylation of 4E-BP1, mTOR and GSK-3ß in younger rats and decreased the phosphorylation of these molecules in the older rats. The “mTOR”- mediated phosphorylation of p70S6k (THR 389) decreased in all the three age groups in the EDL, while “ERK1/2”- mediated phosphorylation of p70S6k (THR421/SER424) increased in all the three age groups in the EDL, but increased only in the aged in soleus. Conversely, SHP-2 phosphorylation decreased in the aged soleus. Taken together, these data imply that aging affects the expression, basal phosphorylation and mechanical regulation of different signaling molecules in the rat EDL and soleus.