16.    Age-associated alterations in human scalp hair follicle melanocytes –an in vitro study.
Sobia Kauser(1), Gillian Westgate(2), Martin Green (3)1.Medical Biosciences, School of Life Sciences, University of Bradford, Bradford, West Yorkshire BD7 1DP, UK. 2.Westgate Consultancy, Stevington, Bedfordshire, UK. 3.Unilever R&D Colworth, Sharnbrook, Bedford, UK

Gradual loss of skin pigmentation with age is associated with a slow decrease in epidermal melanocyte numbers. By contrast, loss of melanocytes in ageing hair follicles (HF) is more abrupt, suggesting a different “melanogenetic clock” in the latter. Hair graying (canities) is thought to result from an increase in reactive oxygen species (ROS)-associated damage and accumulated oxidative stress in HF melanocytes, coupled with an age-related depletion of the HF melanocyte reservoir, and/or defective cell activation/migration during the cyclic repopulation of successive new anagen hair bulbs. To clarify the mechanism of canities we examined age-associated change in HF melanocyte proliferation and in levels of expression of key melanogenic enzymes and catalase in matched epidermal melanocyte (EM) and hair follicle melanocyte (HFM) cultures derived from young, mid-aged and older donors. This study showed that HFM have a greater proliferative potential than matched EM at all ages. By contrast, the age-related decrease in proliferation was greater in HFM than in matched EM. Moreover, while the expression of gp100, Tyrosinase, Tyrosinase-related protein (TRP)-1 and TRP-2 in vitro also decreased with age, the age-associated down-regulation of the former was greater in HFM than in EM. The exception was TRP-2, which was up-regulated in HFM of aged donors. The level of expression of anti-oxidant enzyme catalase was similar in matched HFM and EM from younger donors but showed an age-dependent down-regulation in expression. Strikingly, a greater decrease in expression was detected in HFM than in matched EM derived from aged donors. In summary, the age-dependant decrease in melanocyte proliferation in vitro and the differential age-associated down-regulation of melanogenic enzymes in HFM vs EM suggests that these melanocyte sub-populations are differentially regulated. The decrease in catalase expression with age further suggests that disruption of anti-oxidant defence mechanisms in melanocytes may contribute to loss of pigmentation with age.