Premature Senescence of Balding Dermal Papilla Cells In Vitro Is Associated with p16INK4a Expression

Abstract

Androgenetic alopecia (AGA), a hereditary disorder that involves the progressive thinning of hair in a defined pattern, is driven by androgens. The hair follicle dermal papilla (DP) expresses androgen receptors (AR) and plays an important role in the control of normal hair growth. In AGA, it has been proposed that the inhibitory actions of androgens are mediated via the DP although the molecular nature of these interactions is poorly understood. To investigate mechanisms of AGA, we cultured DP cells (DPC) from balding and non-balding scalp and confirmed previous reports that balding DPC grow slower in vitro than non-balding DPC. Loss of proliferative capacity of balding DPC was associated with changes in cell morphology, expression of senescence-associated beta-galactosidase, as well as decreased expression of proliferating cell nuclear antigen and Bmi-1; upregulation of p16(INK4a)/pRb and nuclear expression of markers of oxidative stress and DNA damage including heat shock protein-27, super oxide dismutase catalase, ataxia-telangiectasia-mutated kinase (ATM), and ATM- and Rad3-related protein. Premature senescence of balding DPC in vitro in association with expression of p16(INK4a)/pRB suggests that balding DPC are sensitive to environmental stress and identifies alternative pathways that could lead to novel therapeutic strategies for treatment of AGA.

Regulation of skin aging and heart development by TAp63

“…Recent studies reported a dermal stem cell depletion with aging 53 and a premature senescence of the dermal papilla cell in balding scalps. 54 Nevertheless, what could be the role of TAp63 in these processes? What would be the optimal level of manipulation of TAp63 in the SKPs as we age?…”

Controlled clinical trial for evaluation of hair growth with low dose cyclical nutrition therapy in men and women without the use of finasteride

“…Though siblings carry the genes, there are more collaborators than just the presence of DHT to manifest miniaturization and present the clinical characteristics of AGA. Works of Headington, Philpott, Farjo N, Farjo B and Bahta have indicated that the multiple pathways of hair loss are in fact, interlinked, overlapping and in over 33% of the cases there may not be any identifiable cause [6,28] . DHT has been considered to be a cause for hair loss but it is uncommon to find raised DHT levels in patients and there is no correlation between DHT levels and the grade of hair loss manifested in the patients [18] .…”

Analysis of changes in microRNA expression profiles in response to the troxerutin-mediated antioxidant effect in human dermal papilla cells

“…Furthermore, DP cells in the balding scalp grow more slowly in vitro, compared with cells from the non-balding scalp. The reduced proliferative activity of balding DP cells is associated with changes in the expression levels of senescence-associated (SA) β-galactosidase, oxidative stress markers, superoxide dismutase and catalase (20). These findings indicate that oxidative stress is important in the loss of DP cells and in hair production.…”