Growth arrest-specific 6 (GAS6) protein successfully reversed aging in human umbilical cord mesenchymal stem cells by activating the PI3K/Akt pathway, which promoted p62 accumulation and Keap1 degradation, ultimately allowing Nrf2 to enter cell nuclei and activate antioxidant genes. This cascade prevented cellular senescence and restored angiogenic capacity in aged stem cells used for diabetic wound therapy. The finding addresses a critical bottleneck in regenerative medicine: stem cells inevitably age during laboratory expansion, losing their therapeutic potency. Current diabetic foot ulcer treatments often fail, leaving patients at risk for amputation. This research suggests GAS6 could serve as a cellular rejuvenation factor, potentially extending the therapeutic window for stem cell therapies. The mechanistic clarity—linking autophagy regulation to antioxidant activation—provides multiple intervention points. However, the study used laboratory-cultured cells and animal models, requiring human clinical validation. The approach represents an incremental but practically significant advance in addressing one of diabetes's most devastating complications, potentially transforming how aged or senescent stem cells are prepared for therapeutic use.