Sarcopenia involves coordinated disruption of multiple biological programs, yet most pharmacological studies target single pathways. Here we mapped the transcriptomic effects of ginsenoside Rb2 in D-galactose-induced aging of C2C12 myotubes and validated findings against human skeletal muscle single-nucleus RNA-seq from aged donors. Bulk RNA-seq across four red ginseng fractions (water extract, saponin-rich fraction, Rb2, and non-saponin fraction) identified a shared translational and proteostatic rescue signature alongside a saponin-specific lipid/sterol regulatory axis. Rb2 alone reversed 91% of D-galactose-co-modulated genes. To separate aging-relevant from model-specific responses, we applied sequential cross-species filtering to 1,348 Rb2-responsive pathways, revealing that 770 were associated with human aging, 402 showed directional concordance with the D-galactose model, and 329 were reversed by Rb2. These validated pathways converged on three biological axes (extracellular matrix remodeling, inflammatory signaling, and lipid metabolism) and were resolved predominantly to endothelial cells and fibro-adipogenic progenitors in the human aging atlas. These findings establish Rb2 as a multi-axis transcriptomic reversal agent for skeletal muscle aging and demonstrate that cross-species filtering can distinguish genuine aging signals from cell-culture artifacts in pharmacological transcriptomics.