R. Baker¹, R. Williams¹, G.E. Westgate¹, A.D. Pawlus², J. Zguris², M.J. Thornton¹

1 – Centre for Skin Sciences, Faculty of Life Sciences, University of Bradford, Bradford, UK
2 – Aveda, Hair Innovation & Technology, Minneapolis, USA

With age, female scalp undergoes significant structural and molecular changes. We previously reported the dermal environment impacts the ageing hair follicle (Williams et al, J Invest Dermatol, 141: 1041-1051; 2021). We hypothesise this is a key driver of the hair ageing phenotype.

Using single cell RNA sequencing and proteomics we compared early passage (P3) dermal sheath (DS) and dermal papilla (DP) cells cultured from young (20-23yrs) and older (57-77yrs) female scalp.

Differences in the aged DS transcriptome included diminished DS signature genes, mesenchymal, vascularization and contractibility genes, with increased expression of senescence-associated genes. Contraction-related proteins e.g., smoothelin were also reduced with age. Differences in the aged DP transcriptome highlighted lower expression of genes related to hair follicle cycle oscillators, e.g., endoglin, and inhibitors of differentiation e.g. ID2 and ID3. Proteomic analysis confirmed a significantly number of differentially expressed proteins in DP cells (290) compared to DS cells (11) between the two age groups. Cell Chat pathway analysis of the single cell RNA sequencing data identified alterations to the intercellular signalling between old and young populations of DS and DP cells. The signalling strength of GAS6, Osteopontin, NOTCH and Prostaglandin signalling pathways was notably altered with age in the DS cells. Analysis of the DP cells indicated alterations to the GAS6, WNT, Prostaglandin, Midkine and CD46 pathways with increasing age.

Loss of DS signature, including contractibility, suggests a reduced mechanical capacity to support a terminal hair follicle and remodeling during anagen and catagen. The significantly greater diversity in ageing DP cell populations compared to DS cells, highlight the molecular and functional differences between these two specialized hair follicle fibroblasts, and underline the importance of the DP in driving signals regulating hair follicle oscillation and cycling.