Our Skin Tone Rainbow PDF

Our skin tone rainbow Mignon Cristofoli 1 Overview evolution folate Vit D melanocytes and melanin pigmentation in skin with darker tones (dark pigmentation or DP) or lighter tones (low pigmentation or LP) aging general solar radiation: UV, visible & infrar...

Our skin tone rainbow Mignon Cristofoli 1 Overview evolution folate Vit D melanocytes and melanin pigmentation in skin with darker tones (dark pigmentation or DP) or lighter tones (low pigmentation or LP) aging general solar radiation: UV, visible & infrared photoaging: elastin, collagen, dermal-epidermal junction photoprotection and treatments for DP skin 2  Primates Great apes Our family tree (Homo heidelbergensis, Neanderthals, chimpanzees, gorillas etc) The species that human beings belong to is known as Homo sapiens We began to evolve ± 300 000 years ago, developing lighter skeletons and larger brains than other early humans Fossils and DNA have confirmed that humans are one of more than 200 species belonging to the order of Primates. Within this larger group, humans are categorised within a sub-group known as the great ape family. Although we did not evolve from any of the apes living today, we share characteristics with chimpanzees, gorillas, and orangutans (the great apes), as well as other apes. It is believed that we evolved from Homo This is not accurate - but gives a little taste of heidelbergensis, the common ancestor we share with our evolution (generated using AI) Neanderthals, who are our closest extinct relatives. https://humanorigins.si.edu/evidence/human-fossils/species/homo- sapiens#:~:text=The%20species%20that%20you%20and,Homo%20sapiens%20evolved%20in%20Africa. 3 The evolution…. Like many mammals, primates have hair covering most of their bodies Humans are distinguished by their lack of fur Our surface area is covered with almost invisible vellus hairs - and we are therefore referred to as “functionally naked” Remnants of primate hair coat occurs in localised areas eg head, armpit, pubic region Evidence suggests that our “hair loss” was the result of natural selection: to improve our thermoregulation as we participated in intense physical activity in very high heat environments This resulted in the loss of most of our body hair, combined with an increase in the coverage and density Vellus hair of eccrine sweat glands to assist with the potential for heat loss via evaporation from the surface of the skin Disadvantages: loss of protection from (i) abrasion and (ii) UV radiation 4 The evolution continued…. Consequential changes included the accelerated evolution of keratinisation and epidermal differential genes that have contributed to enhance barrier functions Genomic evidence has also indicated that the evolution of permanent, dark, eumelanin-rich skin pigmentation coincided with development of hairlessness and increase in eccrine glands Why do you think this happened? 5 The evolution continued…. Strongest hypothesis is that eumelanin- rich pigmentation protected against the photodegradation of folate in the dermal vasculature- which is important for fertility deficiencies are associated with potentially fatal birth defects as well as male infertility. (Folate is also important in DNA biosynthesis, repair, amino acid metabolism, melanin production & thermoregulation). 6 What about changes to skin pigmentation? What caused changes to our dark pigmentation? If the 300 000 years of human evolution were converted into 1 year, changes to darker skin colour would have happened this week : “Desmond Tobin” Migration of Homo sapiens began ± 55 000 years ago and this created a deficiency of Vit D Vit D regulates calcium levels (absorptions, storage and retention) Amongst other things, Vit D reduces rickets (children)/ osteomalacia (adults), by helping your body absorb calcium and phosphorous to create strong bones Outside of the equatorial latitudes UVB levels are not high enough to combat the effective sunscreen provided by the eumelanin in dark skin. This inhibits the production and storage of Vit D. Result: near the equator - dark pigmentation for photoprotection nearer the poles - depigmented skin to promote UVB-induced synthesis of Vit D intermediate latitudes with seasonal high loads of UVB - evolution of intermediate colour, skin capable of tanning and protecting when required. 7 Our skin is more than a protective barrier Flexible, but robust Provides barrier functions including Protection against * Some forms of radiation * Viruses, bacteria, other exogenous substances Waterproof covering Prevents dehydration One of the 5 senses: touch Regulates body temperature Sweat Traps heat 8 A reminder of the cells in the epidermis Keratinocytes ± 95% Langerhans cells ± 2% Merkel cells ± 0.5% Melanocytes make up around 3% of cells in the epidermis 1:36 ratio of melanocytes to viable keratinocytes: this is also known as an epidermal melanin unit 9 Melanocytes & melanin melanocytes exist in the basal layer of the epidermis melanin is synthesised in melanocytes and transferred to viable keratinocytes everyone has the same number of melanocytes pigmentary variations are due to: number of melanin granules (melanosomes) produced per melanocyte melanin content of the granules types of melanin pigment: eumelanin (brown-black) or pheomelanin (yellow-red) can be contained in separate or the same melanosome distribution of melanin granules in the epidermis Darker skins: more eumelanin per granule, only ± 2-8% pheomelanin, more melanin granules delivered to keratinocytes 10 Synthesis of melanin Melanin is all derived from the amino acid L- Tyrosine Synthesis requires three enzymes: tyrosinase, tyrosinase-related protein 1 and tyrosinase- Goncalves, et al 2023. related protein 2 Synthesis affected by pH - optimal is pH 6.8; Caucasian pH is more acidic, while darker skins are closer to neutral enhancing tyrosinase activity Distribution of melanin - and supra & melanin synthesis by up to 10-fold more nuclear caps Mature melanosomes move along dendrites to the keratinocytes where they are taken into the cell and distributed around the nucleus creating supra-nuclear caps, also known as a melanosome microparasol (Byers et al, 2003 ) Dendrites allow melanocytes to distribute melanin to any viable keratinocytes in the epidermis 11 Hurbain, I., Romao, M., Sextius, P., Bourreau, E., Marchal, C., Bernerd, F., Duval, C. and Raposo, G., 2018. Melanosome distribution in keratinocytes in different skin types: melanosome clusters are not degradative organelles. Journal of Investigative Dermatology, 138(3), pp.647-656. 12 Melanocytes & melanin In general melanocytes are involved in the protection of keratinocytes from UV damage eg to DNA However, in relation to photoaging: eumelanin is protective, while pheomelanin is phototoxic (produces ROS, meaning that skin rich in pheomelanin is at particular risk for UV related cancers) Darker skins with higher eumelanin content and more granules (melanosomes) offer greater levels of photoprotection Higher levels of melanin are detected in photo-exposed versus photo-protected parts of the body 13 ROS: reactive oxidation species  Skin-typing: Fitzpatrick Skin Phototype Classification “Skin-typing” systems developed to predict photobiological responses Fitzpatrick Skin Phototype Classification (FSPC) developed in 1975 to determine the appropriate doses of UVA in conjunction with psoralen in treatments for vitiligo, eczema etc Prior to FSPC, doses were based on hair and eye colour FSPC initially only applied to individuals with lighter skin tones (types I - IV) Extended in 1988 to darker tones (V - VI) These 2 additional tones are not sufficient to describe the range of darker skin tones and can lead to many inaccuracies when phototyping 14  Skin-typing: Individual Typology Angle (ITA) ITA assesses actual pigmentation based on colorimetry ITA categorises skin types into six categories, from very light to dark skin. The higher the ITA, the lighter the skin: very light (> 55°), light (41° to < 55°), intermediate (28° to < 41°), tan (10° to < 28°), brown (−30° to < 10°) and dark (< −30°). An ITA < 28° corresponds to darker skin phototypes Krutmann et al, 2023 15  Pigmentation and photoprotection DNA damage due to sun exposure is reduced by a factor of three in dark (highly pigmented) v light (low pigmentation) skin Studies that compared skin cancer in white/ Caucasian skin and the skin of black African-Americans, they found much higher rates of skin cancer in Caucasian skin, reflecting the protection derived from pigmentation (to UVR exposure) Why? It was found that highly pigmented skin Hurbain et al, 2018 provided 59 times the protection in the basal layer of the epidermis (relative to ITA (individual typological angle) classification of skin low pigmented skin) colour phenotypes - more objective than Fitzpatrick scale 16  Non - pigmentary differences in DP and LP skin differences in dermal-epidermal junction: more regular and pronounced rete ridges (DP) more area of contact between epidermis (avascular) and dermis (vascular) => improved transfer of nutrients (DP) dermal protein composition: monocyte chemotactic protein-I (MCP-1) is found to a greater extent in DP skin - although important in wound healing are also linked to keloids post-inflammatory hyperpigmentation are more common indicators of aging in DP skin than wrinkles some differences are inherent to skin of colour (eg rete ridges), others are attributable Watson et al, 2019 to the long-term photo-protective effects of melanin (i.e. photo-damage is less marked DP: darkly pigmented skin, LP lightly pigmented skin than in Caucasian skin) 17 Aging - general Factors that affect aging of the skin Intrinsic how the passing years affect you. It is evident in photo-protected body sites Extrinsic Impact of environmental factors including smoking, diet, pollution, trauma, UV, visible and infrared light irradiation (i.e. photoaging). Noticed predominantly on face, neck and arms. Many features of intrinsic and extrinsic aging overlap Photodamage is considered the main determinant of skin aging Picture illustrates the effects of chronic sun exposure Truck driver for 28 years (69 years to one side of the face old) shows the effects of sun damage Gordon, J.R. and Brieva, J.C., 2012. Unilateral dermatoheliosis. New England Journal of 18 Medicine, 366(16), p.e25. Aging - intrinsic Caucasian skin Instrinsic aging in Caucasian skin is associated with the following changes: decrease in melanocytes and Langerhans cells (leading to an increase in skin cancers) DP skins also exhibit a reduction in melanocytes, together with an increase in dermal melanophages -results in dyspigmentation due to photo-exposure sebaceous glands increase in size, resulting in larger pore sizes despite this, sebum secretion is reduced Increase in collagen degrading MMPs (matrix metalloproteinases) fibroblast proliferation decreases Collagen decreases and ratio of Collagen type III: type I increases 19  Solar radiation: UV UV radiation is a major factor in skin aging ± 7% of all solar radiation UVA (320-400 nm), UVB (290 - 320 nm), UVC (200 - 290 nm) UVC is filtered out by the ozone layer => not relevant to the skin Longer wavelength => deeper penetration Shorter wavelength => higher frequency/ intensity/ energy UVB affects mainly the epidermis and superficial dermis UVA can reach mid dermis UVB has been associated with sun burn/ tanning and skin cancers UVA is mainly implicated in aging, but also causes indirect DNA damage Ash et al, 2017 Light penetration from various wavelengths 20  Solar radiation: UV UVB is 1000 x more erythemogenic than UVA DP skin estimated intrinsic SPF of ± 13.4 Schmid et al, 2017 Melanin provides photoprotection by absorbing the energy from the photons and dissipating it as heat Without this protection our DNA, would be exposed to this high energy. Thymine bases, in particular, are susceptible and can result in covalent bonds => ultimately resulting in mutations UV is filtered 5 x more effectively in DP skin After UV exposure, melanin increase in DP skin ±12%, East Asian skin ± 4% and Caucasian skin ± 1% Mechanisms for pigmentation are greater in DP skin UV also causes ROS, and depletes endogenous antioxidants eg glutathione, tocopherol and ubiquinone UV inflammatory effects include induction of inflammatory cytokines and MMP-1 (which leads to collagen degradation and inhibits collagen synthesis) erythemogenic: causes abnormal redness 21  Solar radiation: visible light (VL) 400 - 760 nm (often 400 -800 nm), longer wavelength = deeper penetration ± 44% of solar radiation reaching the Earth’s surface Melanin is a chromophore that also absorbs all visible light wavelengths As a result, heat is generated. Absorption also leads to vasodilation and appearance of redness (erythema) As darker skin has more melanin, this response is exacerbated (don’t forget there is more VL than UV) VL also leads to increased pigmentation, although UV is 25 times as efficient as VL in inducing the same level of pigmentation VL can cause ROS and upregulation of inflammatory cytokines and MMP-1 - to a lesser extent than UV exposure VL can also potentially give rise to indirect DNA damage 22 Solar radiation: infrared light (IR 760 nm - 1 mm) IRA 760 nm - 1440 nm, IRB 1440 - 3000 nm, IRC 3000 nm - 1 mm, longer wavelength = deeper penetration ± 40% of solar radiation reaching the Earth’s surface IRA & B can penetrate epidermis, dermis and subcutaneous tissue like VL it also has thermal effects, vasodilation in the papillary dermis may result in redness (erythema) IR reaches dermis, therefore affects fibroblasts and does not affect the cells of the epidermis Any resulting pigmentation would therefore have to occur indirectly as a result of thermal effects 23  Photoaging - Elastin Photo-protected skin exhibits normal architecture in contrast to photo-exposed skin where elastin deposition is disorganised Watson et al, 2019 The exposure to sun can result in elastosis, a change to the normal architecture of the elastic fibres The accumulated elastin in the upper dermis of photo-exposed skin is morphologically abnormal and could occupy areas of lost collagen Reduces elasticity of the skin Fibrillin-rich microfibrils, involved with elastin deposition, are susceptible to UV exposure DP skin has been shown to exhibit equivalent elasticity in both sun exposed and sun protected skin sites. This was not the same in Latin American and Caucasian subjects which exhibited reduced elasticity in photo- exposed sites (Berardesca and Maibach, 1996) Transforming growth factor beta (TGF-B), which stimulates fibroblast production & can induce elastin is found in higher levels (together with the TGF-B receptor) in DP skin relative to LP skin Fibroblasts are also larger and more active in DP v LP Increased elastin in DP skin delays the onset of photoaging 24  Photoaging - Collagen In protected skin, type I and III collagen was shown to alter only after the 8th decade In sun-exposed skin the intensity of collagen significantly decreased from 82.5% and 80.4% in the 1st decade to 53.2% and 44.1% in the 9th decade (El‐Domyati et al, 2002) There is a 40% decrease in type III pro-collagen in sun damaged v sun protected skin El‐Domyati et al, 2002; 25 study used 38 Egyptian participants Photoaging - dermal- epidermal junction Rete ridges in young v aged buttock and forearm (FA) show flattening due to age alone (buttock) and age + photo-exposure (FA -forearm) (Newton et al, 2017) The flattening on the dermal epidermal interface (rete ridges) is associated with aging, and this is increased in photoaged skin. Less contact with vascular dermis = less nutrients => greater fragility DP skin: the more pronounced and regular rete ridges, reduce the appearance of aging and also the onset of photoaging 26  Photoaging different responses of DP and LP skins to solar radiation result in differences in aging characteristics i.e. phenotypes are different: LP skins in skin predominantly reflects the impact of extrinsic aging , while DP reflects intrinsic aging DP: wrinkles (rhytides) are delayed by up to 20 years and even then, may be less severe than those of LP skin DP: Facial volume shifts, related to intrinsic aging, are more commonly used to identify aging in DP skin (eg malar fat pad sagging) DP has a higher risk of dyschromias (abnormality in pigmentation), but also occurs in LP DP: gradual decrease in pigmentation with age (decline in melanocytes with age) phenotype: observed characteristics of an individual resulting from interaction of genotype with the environment 27 Photoaging LP skin Two main types of extrinsic aging, described as hypertrophic phenotype (HP) and atrophic phenotype (AP) HP is characterised by deep wrinkles, laxity of the skin, leathery appearance, dyspigmentation, fragile skin, impaired wound healing AP smooth skin with fine wrinkles, spider veins (telangiectasia), depigmentation (loss of pigment), actinic keratosis (dry scaly patches) 28 Photoprotection for DP skin common misconception that DP skin is not at risk for skin cancer as a result, cancers are diagnosed late and there is greater morbidity photoprotection would help prevent dyspigmentation VL and IR may also affect pigmentation effects in DP skin For this reason, physical sunscreens would be best for DP skin white cast effect can be offset by (i) micronising the particles and (ii) adding a pigment => more acceptable Antioxidants may be used to help diminish any ROS and MMPs 29 Treatments for DP skin Uneven skin pigmentation hydroquinone, azelaic acid and kojic acid have been used tretinoin has resulted in contact dermatitis, which in turn can result in hyperpigmentation are however many potential benefits: decreases melanin, more even complexion => reducing effects of photoaging improves papillary dermal collagen => improvement of fine wrinkles improve deeper dermal changes use cream not gel, introduce low amounts and very slowly 30 Conclusion Very broad look at DP v LP skins DP skins: rete ridges offer greater exposure to vasculated dermis = better nutrients aging reflects intrinsic aging more melanin production, protects more against photoaging and skin cancers than LP skin should still use photoprotection - physical sunscreens would be better due to effects of thermal absorption on pigmentation LP skin very susceptible to photoaging aging reflects extrinsic aging have two main types of extrinsic aging : hypertrophic phenotype (HP) and atrophic phenotype (AP) 31 References https://humanorigins.si.edu/evidence/human-fossils/species/homo- sapiens#:~:text=The%20species%20that%20you%20and,Homo%20sapiens%20evolved%20in%20Africa. Ash, C., Dubec, M., Donne, K. and Bashford, T., 2017. Effect of wavelength and beam width on penetration in light- tissue interaction using computational methods. Lasers in medical science, 32, pp.1909-1918. Berardesca, E. and Maibach, H., 1996. Racial differences in skin pathophysiology. Journal of the American Academy of Dermatology, 34(4), pp.667-672. Byers, H.R., Maheshwary, S., Amodeo, D.M. and Dykstra, S.G., 2003. Role of cytoplasmic dynein in perinuclear aggregation of phagocytosed melanosomes and supranuclear melanin cap formation in human keratinocytes. Journal of investigative dermatology, 121(4), pp.813-820. Del Bino, S., Duval, C. and Bernerd, F., 2018. Clinical and biological characterization of skin pigmentation diversity and its consequences on UV impact. International journal of molecular sciences, 19(9), p.2668. El‐Domyati, M., Attia, S., Saleh, F., Brown, D., Birk, D.E., Gasparro, F., Ahmad, H. and Uitto, J., 2002. Intrinsic aging vs. photoaging: a comparative histopathological, immunohistochemical, and ultrastructural study of skin. Experimental dermatology, 11(5), pp.398-405. Goncalves, K., De Los Santos Gomez, P., Costello, L., Smith, L., Mead, H., Simpson, A. and Przyborski, S., 2023. Investigation into the effect of skin tone modulators and exogenous stress on skin pigmentation utilizing a novel bioengineered skin equivalent. Bioengineering & Translational Medicine, 8(2), p.e10415. 32 References Gordon, J.R. and Brieva, J.C., 2012. Unilateral dermatoheliosis. New England Journal of Medicine, 366(16), p.e25. Hurbain, I., Romao, M., Sextius, P., Bourreau, E., Marchal, C., Bernerd, F., Duval, C. and Raposo, G., 2018. Melanosome distribution in keratinocytes in different skin types: melanosome clusters are not degradative organelles. Journal of Investigative Dermatology, 138(3), pp.647-656. Jablonski, N.G. and Chaplin, G., 2017. The colours of humanity: the evolution of pigmentation in the human lineage. Philosophical Transactions of the Royal Society B: Biological Sciences, 372(1724), p.20160349. Jones, P., Lucock, M., Veysey, M. and Beckett, E., 2018. The vitamin D–folate hypothesis as an evolutionary model for skin pigmentation: an update and integration of current ideas. Nutrients, 10(5), p.554. Krutmann, J., Piquero-Casals, J., Morgado-Carrasco, D., Granger, C., Trullàs, C., Passeron, T. and Lim, H.W., 2023. Photoprotection for people with skin of colour: needs and strategies. British Journal of Dermatology, 188(2), pp.168-175. Newton, V.L., Bradley, R.S., Seroul, P., Cherel, M., Griffiths, C.E.M., Rawlings, A.V., Voegeli, R., Watson, R.E.B. and Sherratt, M.J., 2017. Novel approaches to characterize age‐related remodelling of the dermal‐epidermal junction in 2D, 3D and in vivo. Skin Research and Technology, 23(2), pp.131-148. Sathananthan, A.H., 2015. Human Cell and Tissue Fine Structure for Teaching and Research In Stem Cells (Vol. 1). Professor Arunachalam Henry Sathananthan. Schmid, J., Hoenes, K., Rath, M., Vatter, P. and Hessling, M., 2017. UV-C inactivation of Legionella rubrilucens. GMS hygiene and infection control, 12. Watson, R.E. and Griffiths, C.E. eds., 2019. Cutaneous photoaging. Royal Society of Chemistry. (ProQuest Ebook Central, https://ebookcentral.proquest.com/lib/ual/detail.action?docID=5896993). 33 https://www.youtube.com/watch?v=y4c73lLKNPk 34