L2 THE AGING HAIR FOLLICLE PIGMENTARY UNIT - ALL MAY NOT BE LOST
Tobin DJ
Department of Biomedical Sciences, School of Life Sciences, University of Bradford, United Kingdom

As social beings we communicate significantly via our physical appearance and of all our visible features, skin and hair color contribute disproportionately to our overall visual appearance. Moreover, as our average longevity (in the developed Western world) approaches 80 years and more, it is an uncomfortable reality that we will spend an ever-increasing proportion of our lives remote from our youth. In fact most of us will gray long before we reach "middle-age". Exploiting the recent explosion in our understanding of hair follicle biology, biologists have begun to dissect the fascinating life-history of the skin and hair follicle pigmentary units. These studies reveal striking differences in the regulation of the 'melanocyte clocks' within the epidermis and hair follicle and between melanocyte systems located in different anatomic body sites. While much continues to be learned from mouse mutants, perhaps of more relevance to humans are the observations of cutaneous pathologies with associated pigmentary anomalies. For example, why do we see selective damage to the follicular pigmentary unit in alopecia areata, while broadly selective damage to the epidermal pigmentary unit occurs in vitiligo? There is significant interest in the elucidation of mechanisms underlying the "iatrogenic" responses of both pigmentary units to exogenous stimulation, such that aged, melanocyte-poor, skin and hair follicles can be induced to repigment, e.g. after radiation therapy etc. These events suggest the presence of significant plasticity in the melanocyte systems, which likely reflects the retention of melanocyte stem cells after apparent loss of melanocytes from the tissues. Not only are we in need of a more complete understanding of the factors that regulate follicular pigmentation in the fully functioning human hair follicle, we are also relatively ignorant of the molecular mechanisms underpinning melanocyte aging. This lecture will focus on recent research advances from both the murine and human systems including explorations of: newly defined characteristics of the multiple distinct melanocyte sub-populations within the hair follicle and their retention with aging; involvement of CRH and POMC peptides (ACTH, a-MSH, b-endorphin) in human melanocyte phenotype regulation; cross-talk between BMP and POMC peptides in murine hair pigmentation, melanocyte death/ survival during catagen, role of Bcl2 and melanocyte depletion in hair follicles; the importance of the melanocyte master transcriptional regulator Mitf in hair graying and the involvement of reactive oxygen species in the histopathology of canities.