Melanin's impact on skin behaviour: Effects across the pigmentary spectrum.

Variation in skin colour is the most noticeable of human characteristics yet skin's primary functions of sensing and providing protection against our environment are universal. The single most important substance for determining skin colour is the pigment melanin, produced within the skin by cells called melanocytes - and gifted to the surrounding cells of the epidermis, the keratinocytes - to provide protection by filtering ultraviolet radiation (UVR) from the sun. Hence, the level of melanin within our skin not only determines its colour, but also plays a key role in determining the susceptibility of our skin to sun damage. In general, the more melanin there is in the skin, the more UVR can be absorbed, and more protection provided; people with highly pigmented skin have a lower incidence skin cancer than their lighter-skinned peers. Despite these differences, human skin studies aimed at understanding how skin behaves have typically focussed on the skin of white European people and have neglected the biology of more pigmented skin types. In recent years our fundamental knowledge of darker skin has started to expand and it is now clear that in addition to differences in melanin, skin structure and composition differs greatly between those with the lightest and the darkest skin. In this programme, research will focus on expanding this knowledge to truly appreciate the impact of melanin on skin function across the life-course. Our proposed research will assess skin behaviour across all skin tones, from the very lightest to the very darkest, identifying 1) the role of melanin in the organisation of skin tissue; 2) how the epidermis self-renews (through study of epidermal stem cell populations); and, 3) how melanin may confer protection against oxidative stress. Our ultimate goal is to use these learnings to provide better cosmetic products capable of delivering skin benefits which are inclusive to all people, regardless of their age, their sex or the colour of their skin.

Variation in skin colour is the most noticeable of human polymorphisms yet skin's primary functions of maintaining homeostasis, defence against environmental insults (notably solar ultraviolet radiation [UVR]), and mechanical trauma, are universal. Historically, skin research has mostly focussed on white Northern European skin. This programme of research will address variation in skin biology - with a focus on ageing - across the full range of skin pigmentation. Our objectives are to: 1) to assess the impact of constitutive pigmentation on skin structure and function across the entire pigmentary spectrum and to discover if ageing induces convergence to a universal 'aged' phenotype irrespective of pigmentation; 2) to explore if skin melanisation confers a protective effect on epidermal stem cells and whether as a consequence of their preservation is maintenance of epidermal homeostasis retained even in old age; and, 3) to understand if greater skin melanisation confers increased protection against local and systemic oxidative stress and mitochondrial DNA (mtDNA) damage. Using human volunteer studies, we will identify cutaneous changes as a function of age in men and women across the full range of skin pigmentation, using non-invasive biomechanical (cutometry) and physiological (capacitance, trans-epidermal water loss) measures. The project will identify age-dependent cutaneous decline across the full range of skin pigmentation and relate this to the role that epidermal stem cells play in maintaining skin homeostasis. In addition, this study will provide fundamental insight into the underlying mechanistic drivers of skin ageing including the impact of skin pigmentation on protection from UVR, oxidative stress and mtDNA damage. Furthermore, intervention studies using cosmetic products will assess their efficacy in delivering skin benefits that are inclusive to all people, regardless of their age, their sex or the colour of their skin.