1429 Proteomic analysis of cultured dermal papilla, dermal sheath and dermal fibroblast cells from female scalp highlights alterations in the cell populations with increasing age

We have previously reported significant changes with age in female scalp in-situ, and in cultured interfollicular dermal fibroblasts (DF) and dermal sheath (DS) cells’ gene expression (Williams et al, J Invest Dermatol, 141: 2021). We hypothesize that age-related changes in cellular identity alter the hair follicle environment driving hair ageing phenotypes. We have now compared the proteomic profile of primary cultures of DF, DS and dermal papilla (DP) cells from female donors (n=16) age 21-57yrs via 2-way analysis per cell type with age. In DFs, only 11 proteins were significantly differentially expressed in young vs aged cells with an increase in 2 proteins and decrease in 9 with age. In the DS, there were also 11 significantly differentially expressed proteins that altered with age, 8 significantly increased and 3 decreased. However, surprisingly, in the DP, 290 proteins were significantly altered with age, 231 increased and 59 decreased. These findings suggest much greater diversity in the DP cells with ageing, perhaps linking the changes in this niche with hair fibre ageing changes. Comparison of the different cell types also illustrated significantly different protein signatures between the cell types, with a large net gain of new protein expression in the DP with age and more stable proteomes in DS and DF with fewer age-related changes. Gene Ontology and STRING analysis of the data revealed modifications to key pathways in each cell type with increasing age. Modifications to DF elastic fibre formation and metabolic markers, DS basement membrane interactions, and DP angiogenic and protein synthesis pathways were identified. This data highlights the specialized signature of scalp fibroblasts in the hair follicle and interfollicular dermis, and that this identity is significantly altered with age.