Kim JH, Thompson LV. Differential effects of mild therapeutic exercise during a period of inactivity on power generation in soleus type I single fibers with age. J Appl Physiol 112: 1752-1761, 2012. First published March 15, 2012 doi:10.1152/japplphysiol.01077.2011.-The purpose of this study was to investigate the effects of mild therapeutic exercise (treadmill) in preventing the inactivity-induced alterations in contractile properties (e.g., power, force, and velocity) of type I soleus single fibers in three different age groups. Young adult (5-to 12-mo-old), middle-aged (24-to 31-mo-old), and old (32-to 40-mo-old) F344BNF1 rats were randomly assigned to three experimental groups: weightbearing control (CON), non-weight bearing (NWB), and NWB with exercise (NWBX). NWB rats were hindlimb suspended for 2 wk, representing inactivity. The NWBX rats were hindlimb suspended for 2 wk and received therapeutic exercise on a treadmill four times a day for 15 min each. Peak power and isometric maximal force were reduced following hindlimb suspension (HS) in all three age groups. HS decreased fiber diameter in young adult and old rats (Ϫ21 and Ϫ12%, respectively). Specific tension (isometric maximal force/cross-sectional area) was significantly reduced in both the middle-aged (Ϫ36%) and old (Ϫ23%) rats. The effects of the mild therapeutic exercise program on fiber diameter and contractile properties were age specific. Mild treadmill therapeutic exercise attenuated the HS-induced reduction in fiber diameter (ϩ17%, 93% level of CON group) and peak power (N·fiber length·s Ϫ1 ) (ϩ46%, 63% level of CON group) in young adult rats. In the middle-aged animals, this exercise protocol improved peak power (ϩ60%, 100% level of CON group) and normalized power (kN·m Ϫ2 ·fiber length·s Ϫ1 ) (ϩ45%, 108% level of CON group). Interestingly, treadmill exercise resulted in a further reduction in shortening velocity (Ϫ42%, 67% level of CON group) and specific tension (Ϫ29%, 55% level of CON group) in the old animals. These results suggest that mild treadmill exercise is beneficial in attenuating and preventing inactivity-induced decline in peak power of type I soleus single fibers in young adult and middle-aged animals, respectively. However, this exercise program does not prevent the HS-induced decline in muscle function in the old animals.