Age-related changes in female scalp dermal sheath and dermal fibroblasts: how the hair follicle environment impacts hair ageing.

In women, ageing leads to reduced hair density and thinner fibers and can result in female pattern hair loss (FPHL). However, the impact of the ageing dermal environment on female scalp hair follicles (HFs) remains unclear. Here we document in situ changes in 22 women (19-81yrs), and in primary cultures of dermal fibroblast (DF) and dermal sheath (DS) cells. In situ, the papillary/reticular boundary was indistinguishable in young scalp, but prominent over 40yrs, accompanied by reduced podoplanin (PDPN) expression, increased versican (VCAN) expression, and changes in collagen organisation. HFs were shorter, not reaching the adipose layer. Hyaluronic acid synthase 2 (HAS2) was highly expressed, while matrix metalloproteinase-1 (MMP1) was elevated in the DP and DS in situ. Primary DF cultures confirmed MMP1 increased with age, while in DS cells, HAS2 and PDPN increased and α-smooth muscle actin (αSMA) decreased. Both exhibited increased cartilage oligomeric protein (COMP) expression. Proteomics revealed an increase in DS proteins in the DF secretome with age. In summary, ageing female scalp shows striking structural and biological changes in the HF environment that may impact hair growth.