Hair cycle and hair pigmentation: dynamic interactions and changes associated with aging

The tight coupling of hair follicle melanogenesis to the hair growth cycle dramatically distinguishes follicular melanogenesis from the continuous melanogenesis of the epidermis. Cyclic re-construction of an intact hair follicle pigmentary unit occurs optimally in all scalp hair follicles during only the first 10 hair cycles, i.e. by approximately 40 years of age. Thereafter there appears to be a genetically regulated exhaustion of the pigmentary potential of each individual hair follicle leading to the formation of true gray and white hair. Pigment dilution results primarily from a reduction in tyrosinase activity within hair bulbar melanocytes. Thereafter, sub-optimal melanocyte-cortical keratinocyte interactions, and defective migration of melanocytes from a reservoir in the upper outer root sheath to the pigment-permitting microenvironment close to the follicular papilla of the hair bulb, will all disrupt normal function of the pigmentary unit. Evidence from studies on epidermal melanocyte aging suggest that reactive oxygen species-mediated damage to nuclear and mitochondrial DNA may lead to mutation accumulation in bulbar melanocytes. Parallel dysregulation of anti-oxidant mechanisms or pro/anti-apoptotic factors is also likely to occur within the cells. Pigment loss in canities may also affect keratinocyte proliferation and differentiation, providing the tantalizing suggestion that melanocytes in the hair follicle contribute far more that packages of pigment alone. Here, we review the current state of knowledge of the development, regulation and control of the aging human hair follicle pigmentary system in relation with hair cycling. The exploitation of recently available methodologies to manipulate hair follicle melanocytes in vitro, and the observations that melanocytes remain in senile white hair follicles that can be induced to pigment in culture, raises the possibility of someday reversing canities. The perspective of rejuvenation of the whole hair follicle apparatus are still part of the dream but optimising its functional properties is clinically relevant and is close to reality. Finally as hair color influences its visibility when optical methods such as scalp photography are used to count hair fibers, the attention is drawn to possible interpretations of statistically significant changes in visible hair. Such changes may not exclusively be related to improved hair growth itself but also to changes in natural hair color that makes the hair more visible with the method used to count hairs.