Does geographic ancestry influence how skin ages? Abigail K Langton PhD Centre for Dermatology Research The University of Manchester

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Does geographic ancestry influence how skin ages? Abigail K Langton PhD Centre for Dermatology Research The University of Manchester Manchester Institute for Collaborative Research on Ageing (MICRA) 11 th March 2016

Skin pigmentation is perhaps the most obvious example of diversity in human populations. Human skin, regardless of colour, plays a vital role in protecting us from the environment and preventing excessive water loss.

The majority of the world s population consists of people with highlypigmented skin; Despite this, fundamental skin biology research has primarily focussed on white Caucasian skin.

Mechanisms of skin ageing Human skin ageing appears to be the product of two biological processes: 1. The passage of time or intrinsic skin ageing; & 2. Exposure to environmental influences or extrinsic skin ageing. The major extrinsic insults include chronic exposure to solar ultraviolet radiation (photoageing), smoking and pollution.

Clinical manifestations of skin ageing Intrinsic Ageing Photoageing photoaged skin Fine wrinkling Smooth texture Coarse wrinkling Roughened texture Clear complexion Sallow complexion Uniform pigmentation Mottled pigmentation intrinsically aged skin Image from Watson & Griffiths, 2005 Gradual loss of elasticity Marked loss of elasticity and recoil

Photoageing is caused by chronic UVR exposure superimposed onto a background of intrinsic ageing; Unlike sunburn and suntan, which manifest within hours and days, respectively, after a sufficient exposure to UV light, photoageing develops gradually over decades; Chronic sun exposure is estimated to be responsible for around 80% of the effects of facial skin ageing. sunburn Intrinsic ageing of upper inner arm Photoageing of hand

There appears to be variation in how skin ages when individuals of different geographic ancestry are compared. Individuals with lightly-pigmented skin are more susceptible to solar UV-induced skin damage than individuals with highly-pigmented skin.

Suitable for all ethnicities This phase is a common marketing tool for cosmetic companies; Should we be aiming to create personalised cosmetics that target the consumer with regard to both their age and geographic ancestry?

The structure of the skin epidermis dermal-epidermal junction rete ridge dermis Human skin consists of two distinct anatomical regions: a superficial cellrich compartment, the epidermis and a deeper extracellular matrix (ECM)- rich compartment, the dermis. The dermal epidermal junction (DEJ) marks the interface between the epidermis and dermis; Rete ridges strengthen the connection between the two compartments, providing strong adhesion and mechanical support.

Dermal extracellular matrix Changes in the abundance or arrangement of these components can cause changes to the structure and function of the skin. Naylor, Watson & Sherratt, Maturitas (2011)

Aside from the lack of skin pigment, is the assumption that skin is structurally and functionally the same regardless of geographic ancestry correct?

Caucasians; n = 7; 18-29 yrs, Far-East Asians; n = 7; 19-27 yrs, African/African-Caribbeans; n = 7; 18-28 yrs, 6mm punch biopsy from photoprotected buttock.

The epidermis of African skin is thicker, with deeper rete ridges and a more convoluted DEJ than Caucasian and Far-East Asian skin ** ** * * * ** * **

The protein composition of the DEJ is collagen VII-poor in African and Far-East Asian skin compared to Caucasians * ** **

The dermis of African skin is enriched in fibrillar collagen I compared to Caucasians *

The dermis of African skin is enriched in fibrillar collagen III compared to Caucasians *

The dermis of African skin is elastin-poor compared to Caucasians *

African dermis is abundant in both fibrillin-rich microfibrils and fibulin-5 compared to Caucasian and Far-East Asian skin ** ** ** ** **

Conclusions Fundamental differences exist in skin structure and composition in individuals of diverse geographical ancestry; These differences are likely to impact on the primary functions of skin, which are to resist the pressures of UVR, mechanical stress and the propensity for injury and infection; Cosmetic products should be targeting consumers based on their geographic ancestry; Further research into the clinical consequences of these differences in ageing is warranted.

Geographical ancestry and skin ageing Obvious differences in the appearance of skin in aged individuals of different geographic ancestry; In black African skin, ageing appears to manifest at a slower rate and with less of the coarse wrinkling as is apparent in Caucasians. We have now started a collaboration with colleagues based in the USA (Johns Hopkins Medical School) to assess the changes in epidermal structure and dermal composition of aged skin from both sun-protected and sun-exposed body sites.

Photoaged Forearm Sun-exposed Forearm Sun-protected Buttock African Caucasian 42.3% **** 25.9% 41.0% **** 19.0%?

How is your skin ageing? Healthy volunteers aged 18 years or over required for skin research studies You will be paid up to 150 for your time and inconvenience If you are interested in taking part please contact: Abigail on 0161 306 0681 abigail.langton@manchester.ac.uk UREC ref: 14161

Many thanks to all the Volunteers & Research Nurses who made this study possible. Dr Rachel Watson Dr Michael Sherratt Professor Chris Griffiths