This study provides compelling evidence for distinct molecular events contributing to alopecia that may pave the way for new therapeutic approaches.

The current findings demonstrate the ability of the biomimetic PTP20 peptide to preserve the function of follicular melanocytes. The present results suggest potential cosmetic application of this newly designed agonist of α-MSH to promote hair pigmentation and thus, reduce the hair greying process.

We previously showed that topical application of hexoses such as fructose accelerates stratum corneum barrier recovery after barrier disruption. We also showed that various hexoses and polyols interact with phospholipids and decrease the phase transition temperature from the liquid crystal to the crystal phase; i.e., they stabilize the fluid phase of lipids at low temperature. In the present study, we confirmed that topical application of xylitol aqueous solution on human skin after tape stripping accelerated barrier recovery. We next examined changes of lipid fluidity in an epidermal-equivalent model after the application of water and aqueous solutions of xylitol and fructose. For this purpose, we used Laurdan, an environmentally sensitive fluorescence dye, as an indicator of lipid fluidity and observed its emission spectrum with a two-photon microscope. Application of xylitol and/or fructose aqueous solution increased the lipid fluidity of the stratum granulosum layer compared to water application. These results indicate that topical application of certain hexoses or polyols increases the lipid fluidity at the uppermost layer of the stratum granulosum, accelerates the release of lipid from the stratum granular layer, and improves epidermal barrier homeostasis. 627 Fluctuation of Caspase 14 caused by temperature and humidity unbalances the NMF production pathway and the process of keratinocyte enucleation

No abstract

Organismal aging is associated with typical aging phenotypes with structural changes and functional declines of organs. Hair loss is one of the most typical aging phenotypes in mammals, but the underlying mechanisms are still largely unclear. Here we report that the aging of hair follicles progresses in a step-wise manner with a distinct program in hair follicle stem cells (HFSCs) to cause irreversible hair loss. We found that DNA damage response (DDR) in murine HFSCs cause profound proteolysis of type XIIV collagen (COL17A1), a critical molecule for HFSC maintenance. Systematic fate analysis of those primed HFSCs with genetic stem cell tagging demonstrates that they locally initiate an epidermal differentiation program with the induction of c-MYC and NOTCH1, key regulators of epidermal differentiation within the stem cell niche, without renewing themselves or supplying follicular keratinocytes for hair growth. Those cells migrate from the bulge area through the junctional zone toward the epidermis and are eventually desquamated from the epidermal surface. Strikingly, similar aging processes were prematurely induced by Col17a1 deficiency in HFSCs or in progeric mouse models. In addition, we revealed that human scalps gradually cause hair follicle miniaturization by aging and COL17A1 expression is significantly impaired in miniaturized hair follicles through the provocation of COL17A1 protease by DDR. Furthermore, the entire aging program was significantly rescued by the forced maintenance of COL17A1 in HFSCs of aging mice, demonstrating that progression of such tissue aging programs can be controlled through changes in the expression of key molecule COL17A1 in mammalian somatic stem cells.