Uncertainty and sensitivity analysis of hair growth duration in human scalp follicles under normal and alopecic conditions

TL;DR

This study develops and analyzes mathematical models of hair growth cycles under normal, AGA, and AA conditions, revealing differences in uncertainty and key biological processes affecting hair loss.

Contribution

It introduces a comprehensive mathematical framework for hair cycle analysis incorporating experimental data and performs sensitivity analysis across different alopecia conditions.

Findings

Greater uncertainty in hair growth duration in AGA subjects.

In AA, longer hair growth phases are less likely, indicating different underlying dynamics.

MK apoptosis significantly impacts hair growth length in AA but not in AGA or control groups.

Abstract

Hair follicles constantly cycle through phases of growth, regression and rest, as matrix keratinocytes (MKs), the cells producing hair fibers, proliferate, and then undergo spontaneous apoptosis. Damage to MKs and perturbations in their normal dynamics result in a shortened growth phase, leading to hair loss. Two common factors causing such disruption are hormonal imbalance and attacks by the immune system. Androgenetic alopecia (AGA) is hair loss caused by high sensitivity to androgens, and alopecia areata (AA) is hair loss caused by an autoimmune reaction against MKs. In this study, we inform a mathematical model for the human hair cycle with experimental data for the lengths of hair cycle phases available from male control subjects and subjects with AGA. We also, connect a mathematical model for AA with estimates for the duration of hair cycle phases obtained from the literature. Subsequently, with each model we perform parameter screening, uncertainty quantification and global sensitivity analysis and compare the results within and between the control and AGA subject groups as well as among AA, control and AGA conditions. The findings reveal that in AGA subjects there is greater uncertainty associated with the duration of hair growth than in control subjects and that, compared to control and AGA conditions, in AA it is more certain that longer hair growth phase could not be expected. The comparison of results also indicates that in AA lower proliferation of MKs and weaker communication of the dermal papilla with MKs via signaling molecules could be expected than in normal and AGA conditions, and in AA stronger inhibition of MK proliferation by regulatory molecules could be expected than in AGA. Finally, the global sensitivity analysis highlights the process of MK apoptosis as highly impactful for the length of hair growth only in the AA case, but not for control and AGA conditions.