Tissue taurine depletion mediated by knocking out the taurine transporter causes several skeletal muscle abnormalities, including acceleration of cellular aging. In the present study, we investigated the signaling pathway involved in the acceleration of skeletal muscle aging by tissue taurine depletion using the bioinformatic approach of transcriptome data. We previously performed transcriptome analysis on skeletal muscle of taurine transporter knockout (TauTKO) mice using DNA microarray. Bioinformatic analysis of transcriptome data predicted the activation of SMAD3 and β-catenin as upstream signaling molecules of cyclin-dependent kinase inhibitor 2A (CDKN2A, also called p16INK4A), which is a biomarker gene of cellular senescence. The activation of SMAD3 and β-catenin in old TauTKO muscle was verified by western blot analysis. These data indicate that SMAD3- and β-catenin-dependent induction occurs in the TauTKO mouse.