A Wnt5a-Cdc42 Axis Controls Aging and Rejuvenation of Hair-Follicle Stem Cells

The study investigated the role of Wnt signaling in hair follicle stem cells (HFSCs) and its impact on hair regeneration during aging. It was found that aged HFSCs exhibited decreased canonical Wnt signaling and increased non-canonical Wnt5a signaling, which antagonized the former. This shift led to elevated activity and altered distribution of the small RhoGTPase Cdc42 in HFSCs. By using a pharmacological inhibitor called CASIN to suppress the heightened Cdc42 activity, researchers were able to restore canonical Wnt signaling in aged HFSCs. In vivo treatment of aged mice with CASIN promoted the onset of the anagen phase and increased the percentage of anagen skin areas, suggesting that aging-related deficits in HFSCs could be partially reversed through targeted pharmacological interventions.