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Most mammals are coated with pigmented hair. Melanocytes in each hair follicle produce melanin pigments for the hair during each hair cycle. Melanocytes are originally derived from the neural crest and become localized in hair follicles as well as in the epidermis to pigment the hair and skin, respectively. Melanocytes in the epidermis rarely proliferate and produce melanin pigments to protect the skin from ultraviolet light (UV), while melanocytes in hair follicles repeatedly proliferate and differentiate for hair pigmentation in every hair cycle. Once melanocytes colonize the hair matrix at the bottom of each hair follicle during development or during the hair cycle, they differentiate into fully mature melanocytes that produce melanin pigments in an organelle called a melanosome.

Ultrastructural examination of melanocytes in both the epidermis and hair bulb compartments reveals some striking differences between these two closely related melanocyte populations. Differentiated hair bulb melanocytes tend to be larger, more dendritic, have more extensive Golgi and rough endoplasmic reticulum and produce larger melanosomes than their epidermal cousins. Moreover, while melanin granules are almost completely degraded in the differentiating layers of the epidermis, melanin granules transferred into pre-cortical keratinocytes in the hair follicle remain minimally digested as they become locked into the hair fiber from proximal to distal tip.

Each hair cycle is associated with the reconstruction of an intact hair follicle pigmentary unit¼ at least for the first 10 cycles or so. Thereafter, gray and white hairs appear, suggesting an age-related, genetically regulated exhaustion of the pigmentary potential of each individual hair follicle. Melanocyte aging may be associated with reactive oxygen species-mediated damage to nuclear and mitochondrial DNA with resultant accumulation of mutations with age, in addition to dysregulation of anti-oxidant mechanisms or pro/anti-apoptotic factors within the cells.

It has been known that melanocytes in the hair matrix decrease in number in physiologically aged hair follicles. Analysis of the melanocyte stem cells (MelSCs) in mice at different ages revealed that large dendritic melanocytes with abundant melanin pigments appear in the niche with the decrease or disappearance of immature melanoblasts in aging hair follicles. As only immature melanoblasts normally reside in the stem cell niche as MelSCs in non-aged hair follicles, the appearance of melanin-containing dendritic melanocytes is a distinct phenomenon. The changes lead to the eventual complete depletion both of mature melanocytes and of immature melanoblasts in the niche in aged hair follicles, which results in MelSC depletion and subsequent hair greying.