INTRODUCTION Sarcopenia, and the importance of satellite cells (SCs) in muscle growth led us to examine the effects of exercise and age on SC activation and gene expression. METHODS Eight- and 18-month-old mice were either sedentary or underwent 3 weeks of exercise (N = 24). Body mass, distance traveled, and grip strength were recorded at weekly intervals. The extensor digitorum longus (EDL), tibialis anterior (TA), gastrocnemius (GAST), and quadriceps (QUAD) muscles were analyzed along with muscle fiber area, SC activation, neuronal nitric oxide synthase (NOS-I), MyoD, and myostatin protein content. RESULTS Older mice demonstrated decreased body mass, grip strength, and fiber area, but these changes were not affected by exercise. The QUAD muscle from young mice demonstrated an exercise-induced increase in SC activation and NOS-I and downregulation of myostatin. CONCLUSIONS Exercise-induced activation of SCs and regulation of gene expression are muscle-specific and age-dependent. Perturbed sensitivity to exercise in older mice provides insight into sarcopenia and potential treatments.