Age-Related Changes in Female Scalp Dermal Sheath and Dermal Fibroblasts: How the Hair Follicle Environment Impacts Hair Aging

In women, aging leads to reduced hair density and thinner fibers and can result in female-pattern hair loss. However, the impact of the aging dermal environment on female scalp hair follicles remains unclear. In this study, we document in situ changes in 22 women (aged 19-81 years) and primary cultures of dermal fibroblast and dermal sheath cells. In situ, the papillary reticular boundary was indistinguishable in the young scalp but prominent in the scalp of those aged >40 years, accompanied by reduced podoplanin (PDPN) expression, increased versican expression, and changes in collagen organization. Hair follicles were shorter, not reaching the adipose layer. Hyaluronic acid synthase 2 was highly expressed, whereas matrix metalloproteinase 1 was elevated in the dermal papilla and dermal sheath in situ. Primary dermal fibroblast cultures confirmed that matrix metalloproteinase 1 mRNA, MMP1, increased with aging, whereas in dermal sheath cells, hyaluronic acid synthase 2, HAS2, and PDPN increased and alpha-smooth muscle actin alpha SMA mRNA decreased. Both exhibited increased cartilage oligomeric protein, COMP mRNA expression. Proteomics revealed an increase in dermal sheath proteins in the dermal fibroblast secretome with aging. In summary, aging female scalp shows striking structural and biological changes in the hair follicle environment that may impact hair growth.