Sarcopenia is an age-related non-pathological condition that includes a progressive loss of muscle mass, strength and function (Vandervoort et al., 2001). Several factors both intrinsic (metabolic pathway modifications, hormonal and cellular changes) and extrinsic (lifestyle and caloric intake) contribute to sarcopenia. The aging process is associated with a consistent decrease in the ability of muscle tissue to regenerate following injury or overuse due to the impairment of intervening satellite cells (Hawke and Garry, 2001). Satellite cells are muscle stem cells (Charge and Rudnicki, 2004). In response to stimuli such as myotrauma, satellite cells become activated, proliferate, and express myogenic markers and are termed myoblasts. Ultimately, these cells fuse to existing muscle fibers or fuse together to form new myofibers (myotubes) during regeneration of damaged skeletal muscle. Previously we demonstrated that in old subjects the decreased muscle regenerative capability is not due to a reduced number of quiescent satellite cells but, more probably, due to an impairment of their differentiation program (Beccafico et al., 2007; Fulle et al., 2005). Although this cells population was identified 40 years ago, little is known regarding molecular basis of activated elderly satellite cells in muscle repairing process. The aim of the present study was to characterize the transcriptional profile of myoblasts and myotubes obtained from elderly human skeletal muscle biopsies (after informed consent). We have isolated and cultured quiescent satellite cells on which we determined myogenic percentage using immunocytochemistry and the fusion index percentage of myotubes staining fast and slow myosin heavy chains. To obtain the goal, we performed microarray experiments on myoblasts and myotubes at early stages of differentiation (4, 24 and 72 hours) comparing the transcriptional profile of older adults than young individuals. The present study suggest that the failure of the differentiative program is due to the disregulation of genes involved in: i) oxidative damage accumulation in molecular substrates, probably due to impaired antioxidant activity and repair capability (upregulation of polymerase K and SHC1), ii) altered cytoskeleton turnover and extracellular matrix degradation, and iii) activation of atrophy mechanism via a specific FOXO-dependent program as well an impairment of the protein balance.