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This study tests the effect of trimetazidine dihydrochloride (TMZ) on contractility in fast and slow skeletal muscles of adult (Ad, 6-8 mo.) and aged (Ag, 75% lifespan) male (M) and female (F) F344/BN rats. We hypothesized that TMZ would enhance contractility produced by indirect, but not direct, stimulation. Methods: Rats were injected with 3 mg/kg TMZ or vehicle 2x/d x 4 wk. Grip strength was assessed at the start and end of the protocol. Ex vivo force was tested at 4 wks in extensor digitorum longus (EDL) and soleus (SOL) at 3 frequencies (EDL: 1, 30, 120Hz; SOL: 1, 15, 60Hz) of direct/muscle and indirect/nerve stimulation. Fiber type was assessed via myosin heavy chain immunostaining. Results: Indirect vs. Direct Stimulation : Higher forces were seen with direct vs. indirect stimulation (P ≤ 0.002). Only tetanic stimulation (120 & 60 Hz, EDL & SOL, respectively) showed effects of age, sex or TMZ on the ratio of …