Shelterin TPP1 Promotes Hair Regeneration Through Activating Bulge Hair Follicle Stem Cells.

Abstract

Telomere shortening drives hair follicle senescence, yet successful reversal of this aging process has remained elusive. Here, we report that stem cell overexpression of Acd, the gene encoding TPP1 (telomere protection protein 1)-a shelterin component that recruits telomerase-accelerates hair regeneration in mice. Stabilization of TPP1 protein via topical application of TELODIN, a synthetic octapeptide that inhibits TPP1 degradation, similarly promotes hair regeneration. Mechanistically, increased TPP1 mobilizes bulge hair follicle stem cells (bHFSCs) by coordinating telomere capping and telomerase recruitment. By facilitating the synchronization and transition of hair follicles from the quiescent telogen phase to the proliferative anagen phase, TPP1 drives bHFSCs proliferation, differentiation, and migration. These findings identify TPP1 as a master regulator of hair regeneration through telomere capping and elongation, and suggest that topical TELODIN represents a novel therapeutic strategy for advancing hair growth. This work establishes a therapeutic framework for telomere-targeted interventions against alopecia.