Wheat Germ Active Peptide RPPSFF Alleviates Age-Related Osteoporosis through the YY1/AMPK/SIRT1 Pathway.

Wheat germ-derived bioactive peptides have attracted substantial attention for their antioxidant and immunomodulatory properties. However, their potential roles and mechanisms in mitigating osteoporosis remain unclear. This study investigated the antiosteoporotic effects of RPPSFF (RPP), a bioactive peptide isolated from wheat germ, and elucidated its molecular mechanism in maintaining bone homeostasis. Using a mouse model of D-galactose-induced aging and an MC3T3-E1 osteoblast model of senescence, we found that RPP significantly enhanced osteogenesis, inhibited bone resorption, and improved systemic antioxidant capacity and bone microarchitecture. Mechanistic analysis through siRNA-mediated gene silencing, pull-down assay, and molecular docking revealed that RPP directly binds to the transcription factor YY1, thereby activating the AMPK/SIRT1 signaling pathway. These findings indicate that RPP modulates oxidative stress and bone metabolism through the YY1/AMPK/SIRT1 pathway, providing a basis for the development of peptide-based nutritional interventions for age-related osteoporosis.