The following is a summary of “Human Hair Graying Revisited: Principles, Misconceptions, and Key Research Frontiers,” published in the December 2023 issue of Dermatology by Paus et al.

Hair graying is a significant aspect of human physiology and provides a valuable model for investigating pigmentation changes associated with aging. The current understanding suggests that the graying process involves a complex interplay of factors, including cumulative oxidative and DNA damage, heightened mTORC1 activity, melanocyte senescence, and diminished production of pigmentation-related elements within the hair matrix. Multiple regulators influence this process, encompassing genetic elements such as DNA repair deficiencies, IRF4 sequence variations, peripheral clock genes, P-cadherin signaling, neuromodulators, HGF, KIT ligand secretion, and autophagic flux. 

Consequently, these interactions lead to reduced melanogenesis controlled by MITF and tyrosinase, impairment in melanosome transfer to precursor keratinocytes in the hair matrix, and eventual depletion of melanocytes within the hair follicle pigmentary unit (HFPU) and its local progenitors. The irreversible graying phase occurs when melanocyte stem cells in the bulge region are also diminished, which happens at a later stage. The different stages of the hair follicle’s cycling contribute to distinct pigmentary microenvironments, with the early anagen phase being most conducive to melanocyte reintegration and activation. Graying and repigmentation can only manifest during anagen, while the HFPU dismantles in catagen. Notably, temporary reversal of graying has been observed with certain drugs and hormones, indicating potential pathways for targeted intervention. Caution is advised when extrapolating findings from mouse models to human scenarios. Furthermore, the study group delineates unresolved queries and potential future strategies for combating hair graying.

Source: sciencedirect.com/science/article/abs/pii/S0022202X23029627