O#10   The aging hair follicle pigmentary unit - lessons for life and death

Desmond J. Tobin. Dept of Biomedical Sciences, University of Bradford, West Yorkshire, England

Melanin produced by epidermal melanocytes protects human skin by screening harmful ultraviolet radiation. However, the biologic value of hair pigmentation is less clear. In addition to important roles in social/sexual communication, one potential benefit of pigmented scalp hair in humans may be the rapid excretion of heavy metals, chemicals, and toxins from the body by their selective binding to melanin. The primary distinguishing feature of follicular melanogenesis, compared to the continuous melanogenesis in the epidermis, is the tight coupling of hair follicle melanogenesis to the hair growth cycle. Each hair cycle is associated with the re-construction of an intact hair follicle pigmentary unit 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. While the perception of "gray hair" derives in large part from the admixture of pigmented and white hair, it is important to note that individual hair follicles can indeed exhibit pigment dilution or true grayness. This dilution is due to a reduction in tyrosinase activity of hair bulbar melanocytes, sub-optimal melanocyte-cortical keratinocyte interactions, melanocyte death, and defective migration of melanocytes from a reservoir in the upper outer root sheath to the pigmentation-permissive microenvironment close to the follicular papilla. Importantly, melanocytes taken from gray and white hair follicles can be induced to pigment in vitro. Melanocyte aging and death 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. Furthermore, the hair follicle pigmentary unit may be a valuable, highly accessible, model system for the study of neuronal cell aging and neurodegenerative disease. This is supported not only by significant melanocyte and neuronal cell relatedness, but also by the observation that hair follicle melanocyte deletion, after prolonged exposed to melanogenesis-related and keratinocyte metabolism-related oxidative stress, is likely to utilize similar pathways to those utilized by aging/degenerating neuronal cells. Thus the study of age-related changes in the hair follicle pigmentary unit may provide insights into aspects of human health and well-being beyond basic hair color considerations.