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

The study found that hair follicle stem cells (HFSCs) in aged individuals exhibit decreased canonical Wnt signaling and an increase in non-canonical Wnt5a signaling, which negatively affects hair regeneration by delaying the initiation of the growth phase (anagen). This shift in signaling is associated with increased activity and altered distribution of the small RhoGTPase Cdc42 within HFSCs. By treating aged HFSCs with a Cdc42 activity inhibitor called CASIN, researchers were able to restore canonical Wnt signaling, which in turn induced the onset of anagen and increased the percentage of anagen skin areas in aged mice. This suggests that the aging-associated functional deficits in HFSCs can be partially reversed through targeted pharmacological treatments.