The Skin Extracellular Matrix as a Target of Environmental Exposure: Molecular Mechanisms, Prevention and Repair



The dermal extracellular matrix (ECM) undergoes age-related remodelling which leads to wrinkle formation and increased tissue fragility. In healthy young individuals structural ECM assemblies, such as collagens and elastin, are ordered into larger scale structures (collagen fibril bundles and elastic fibres), which mediate the mechanical properties of the dermis. Equally important however, are the less abundant extracellular accessory molecules that regulate complex processes such as cell migration, wound healing and which also orchestrate complex ECM protein-to-protein interactions. These structures and molecular interactions are perturbed in extrinsically aged skin. Using bioinformatics alongside established molecular investigations opens up exciting new ways to understand skin ageing and may help to identify novel biomarkers. In this chapter we propose a mechanism whereby UVR-induced damage of key ECM molecules drives elastosis. We discuss how: i) the amino acid composition of proteins can be used to predict their susceptibility to damage by ultraviolet radiation (UVR) and ii) other environmental factors, such as smoking and air pollution may contribute towards premature skin ageing. Finally this chapter reviews the latest topical applications and systemic therapies that may be able to reverse the consequences of damage to the ECM in ageing.


Skin Ageing Extracellular matrix Ultraviolet radiation Sunscreens Anti-ageing formulations 



This work was supported by a programme Grant from Walgreens Boots Alliance, Nottingham, UK. The authors would like to thank Mr. Matiss Ozols for his contributions to the calculating UVR/ROS and cross-link susceptibility as reported in Tables 5.1 and 5.2.


  1. Abreu-Velez AM, Howard MS (2012) Collagen IV in normal skin and in pathological processes. North Am J Med Sci 4:1–8CrossRefGoogle Scholar
  2. Agache PG, Monneur C, Leveque JL, Derigal J (1980) Mechanical-properties and youngs modulus of human-skin in vivo. Arch Dermatol Res 269:221–232PubMedCrossRefGoogle Scholar
  3. Akhalaya MY, Maksimov GV, Rubin AB, Lademann J, Darvin ME (2014) Molecular action mechanisms of solar infrared radiation and heat on human skin. Ageing Res Rev 16:1–11PubMedCrossRefGoogle Scholar
  4. Allen HB, Johnson BL, Diamond SM (1973) Smokers wrinkles. Jama J Am Med Assoc 225:1067–1069CrossRefGoogle Scholar
  5. Askew EW (2002) Work at high altitude and oxidative stress: antioxidant nutrients. Toxicology 180:107–119PubMedCrossRefGoogle Scholar
  6. Bailey AJ (2001) Molecular mechanisms of ageing in connective tissues. Mech Ageing Dev 122:735–755PubMedCrossRefGoogle Scholar
  7. Baldwin AK, Simpson A, Steer R, Cain SA, Kielty CM (2013) Elastic fibres in health and disease. Expert Rev Mol Med 15:30CrossRefGoogle Scholar
  8. Baranoski S (2000) Skin tears: the enemy of frail skin. Adv Skin Wound Care 13:123–126PubMedGoogle Scholar
  9. Bax DV, Bernard SE, Lomas A, Morgan A, Humphries J, Shuttleworth CA, Humphries MJ, Kielty CM (2003) Cell adhesion to fibrillin-1 molecules and microfibrils is mediated by alpha(5)beta(1) and alpha(v)beta(3) integrins. J Biol Chem 278:34605–34616PubMedCrossRefGoogle Scholar
  10. Bax DV, Rodgers UR, Bilek MMM, Weiss AS (2009) Cell adhesion to tropoelastin is mediated via the C-terminal GRKRK motif and integrin alpha(V)beta(3). J Biol Chem 284:28616–28623PubMedPubMedCentralCrossRefGoogle Scholar
  11. Bedal KB, Grassel S, Oefner PJ, Reinders J, Reichert TE, Bauer R (2014) Collagen XVI induces expression of MMP9 via modulation of AP-1 transcription factors and facilitates invasion of oral squamous cell carcinoma. Plos One 9Google Scholar
  12. Bernstein EF, Underhill CB, Hahn PJ, Brown DB, Uitto J (1996) Chronic sun exposure alters both the content and distribution of dermal glycosaminoglycans. Br J Dermatol 135:255–262PubMedCrossRefGoogle Scholar
  13. Bielefeld KA, Amini-Nik S, Whetstone H, Poon R, Youn A, Wang J, Alman BA (2011) Fibronectin and beta-catenin act in a regulatory loop in dermal fibroblasts to modulate cutaneous healing. J Biol Chem 286:27687–27697PubMedPubMedCentralCrossRefGoogle Scholar
  14. Birk DE, Bruckner P (2005) Collagen suprastructures. In: Collagen, vol 247. Springer, Berlin, pp 185–205Google Scholar
  15. Boyd AS, Stasko T, King LE, Cameron GS, Pearse AD, Gaskell SA (1999) Cigarette smoking-associated elastotic changes in the skin. J Am Acad Dermatol 41:23–26PubMedCrossRefGoogle Scholar
  16. Bradley EJ, Griffiths CEM, Sherratt MJ, Bell M, Watson REB (2015) Over-the-counter anti-ageing topical agents and their ability to protect and repair photoaged skin. Maturitas 80:265–272PubMedCrossRefGoogle Scholar
  17. Brinckmann J, Hunzelmann N, Kahle B, Rohwedel J, Kramer J, Gibson MA, Hubmacher D, Reinhardt DP (2010) Enhanced fibrillin-2 expression is a general feature of wound healing and sclerosis: potential alteration of cell attachment and storage of TGF-beta. Lab Invest 90:739–752PubMedCrossRefGoogle Scholar
  18. Buenger J, Driller H (2004) Ectoin: an effective natural substance to prevent UVA-induced premature photoaging. Skin Pharmacol Physiol 17:232–237PubMedCrossRefGoogle Scholar
  19. Chakraborti S, Mandal M, Das S, Mandal A, Chakraborti T (2003) Regulation of matrix metalloproteinases: an overview. Mol Cell Biochem 253:269–285PubMedCrossRefGoogle Scholar
  20. Chanut-Delalande H, Bonod-Bidaud C, Cogne S, Malbouyres M, Ramirez F, Fichard A, Ruggiero F (2004) Development of a functional skin matrix requires deposition of collagen V heterotrimers. Mol Cell Biol 24:6049–6057PubMedPubMedCentralCrossRefGoogle Scholar
  21. Clarke AW, Wise SG, Cain SA, Kielty CM, Weiss AS (2005) Coacervation is promoted by molecular interactions between the PF2 segment of fibrillin-1 and the domain 4 region of tropoelastin. Biochemistry 44:10271–10281PubMedCrossRefGoogle Scholar
  22. Craven NM, Watson REB, Jones CJP, Shuttleworth CA, Kielty CM, Griffiths CEM (1997) Clinical features of photodamaged human skin are associated with a reduction in collagen VII. Br J Dermatol 137:344–350PubMedCrossRefGoogle Scholar
  23. Daniell HW (1971) Smokers wrinkles—study in epidemiology of crows feet. Ann Intern Med 75:873–880PubMedCrossRefGoogle Scholar
  24. Danielson KG, Baribault H, Holmes DF, Graham H, Kadler KE, Iozzo RV (1997) Targeted disruption of decorin leads to abnormal collagen fibril morphology and skin fragility. J Cell Biol 136:729–743PubMedPubMedCentralCrossRefGoogle Scholar
  25. El-Domyati M, Attia S, Saleh F, Brown D, Birk DE, Gasparro F, Ahmad H, Uitto J (2002) Intrinsic aging vs. photoaging: a comparative histopathological, immunohistochemical, and ultrastructural study of skin. Exp Dermatol 11:398–405PubMedCrossRefGoogle Scholar
  26. Fang M, Liroff KG, Turner AS, Les CM, Orr BG, Holl MMB (2012) Estrogen depletion results in nanoscale morphology changes in dermal collagen. J Invest Dermatol 132:1791–1797PubMedPubMedCentralCrossRefGoogle Scholar
  27. Farwick M, Grether-Beck S, Marini A, Maczkiewitz U, Lange J, Koehler T, Lersch P, Falla T, Felsner I, Brenden H et al (2011) Bioactive tetrapeptide GEKG boosts extracellular matrix formation: in vitro and in vivo molecular and clinical proof. Exp Dermatol 20:602–604PubMedCrossRefGoogle Scholar
  28. Fenske NA, Lober CW (1986) Structural and functional changes of normal aging skin. J Am Acad Dermatol 15:571–585PubMedCrossRefGoogle Scholar
  29. Fisher GJ, Datta SC, Talwar HS, Wang Z-Q, Varani J, Kang S, Voorhees JJ (1996) Molecular basis of sun-induced premature skin ageing and retinoid antagonism. Nature 379:335–339PubMedCrossRefGoogle Scholar
  30. Frances C, Boisnic S, Hartmann DJ, Dautzenberg B, Branchet MC, Lecharpentier Y, Robert L (1991) Changes in the elastic tissue of the non-sun-exposed skin of cigarette smokers. Br J Dermatol 125:43–47PubMedCrossRefGoogle Scholar
  31. Ganceviciene R, Liakou AI, Theodoridis A, Makrantonaki E, Zouboulis CC (2012) Skin anti-aging strategies. Dermato-endocrinology 4:308–319PubMedPubMedCentralCrossRefGoogle Scholar
  32. Geesin J, Murad S, Pinnell SR (1986) Ascorbic-acid stimulates collagen production without altering intracellular degradation in cultured human-skin fibroblasts. Biochim Biophys Acta 886:272–274PubMedCrossRefGoogle Scholar
  33. Geesin JC, Darr D, Kaufman R, Murad S, Pinnell SR (1988) Ascorbic-acid specifically increases type-I and type III procollagen messenger-RNA levels in human-skin fibroblasts. J Invest Dermatol 90:420–424PubMedCrossRefGoogle Scholar
  34. Gigante A, Chillemi C, Greco F (1999) Changes of elastic fibers in musculoskeletal tissues of Marfan syndrome: a possible mechanism of joint laxity and skeletal overgrowth. J Pediatr Orthop 19:283–288PubMedGoogle Scholar
  35. Grassel S, Bauer RJ (2013) Collagen XVI in health and disease. Matrix Biol 32:64–73PubMedCrossRefGoogle Scholar
  36. Green C, Orchard G, Cerio R, Hawk JLM (1998) A clinicopathological study of the effects of topical retinyl propionate cream in skin photoageing. Clin Exp Dermatol 23:162–167PubMedCrossRefGoogle Scholar
  37. Grether-Beck S, Marini A, Jaenicke T, Krutmann J (2014) Photoprotection of human skin beyond ultraviolet radiation. Photodermatol Photoimmunol Photomed 30:167–174PubMedCrossRefGoogle Scholar
  38. Griffiths CEM, Russman AN, Majmudar G, Singer RS, Hamilton TA, Voorhees JJ (1993) Restoration of collagen formation in photodamaged human skin by tretinoin (retinoic acid). N Engl J Med 329:530–535CrossRefPubMedGoogle Scholar
  39. Habashi JP, Judge DP, Holm TM, Cohn RD, Loeys BL, Cooper TK, Myers L, Klein EC, Liu GS, Calvi C et al (2006) Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science 312:117–121PubMedPubMedCentralCrossRefGoogle Scholar
  40. Haftek M, Mac-Mary S, Le Bitoux M-A, Creidi P, Seite S, Rougier A, Humbert P (2008) Clinical, biometric and structural evaluation of the long-term effects of a topical treatment with ascorbic acid and madecassoside in photoaged human skin. Exp Dermatol 17:946–952PubMedCrossRefGoogle Scholar
  41. Haynes SL, Shuttleworth CA, Kielty CM (1997) Keratinocytes express fibrillin and assemble microfibrils: implications for dermal matrix organization. Br J Dermatol 137:17–23PubMedCrossRefGoogle Scholar
  42. Hibbert SA, Watson RE, Gibbs NK, Costello P, Baldock C, Weiss AS, Griffiths CE, Sherratt MJ (2015) A potential role for endogenous proteins as sacrificial sunscreens and antioxidants in human tissues. Redox Biol 5:101–113PubMedPubMedCentralCrossRefGoogle Scholar
  43. Holliday R (2006) Aging is no longer an unsolved problem in biology. In: Rattan S, Kristensen P, Clark BFC (eds) Understanding and modulating aging, vol 1067, pp 1–9Google Scholar
  44. Hoppe U, Bergemann J, Diembeck W, Ennen J, Gohla S, Harris I, Jacob J, Kielholz J, Mei W, Pollet D et al (1999) Coenzyme Q(10), a cutaneous antioxidant and energizer. Biofactors 9:371–378PubMedCrossRefGoogle Scholar
  45. Janeke G, Siefken W, Carstensen S, Springmann G, Bleck O, Steinhart H, Hoger P, Wittern KP, Wenck H, Stab F et al (2003) Role of taurine accumulation in keratinocyte hydration. J Invest Dermatol 121:354–361PubMedCrossRefGoogle Scholar
  46. Jariashvili K, Madhan B, Brodsky B, Kuchava A, Namicheishvili L, Metreveli N (2012) UV damage of collagen: insights from model collagen peptides. Biopolymers 97:189–198PubMedCrossRefGoogle Scholar
  47. Just M, Monso E, Ribera M, Lorenzo JC, Morera J, Ferrandiz C (2005) Relationships between lung function, smoking and morphology of dermal elastic fibres. Exp Dermatol 14:744–751PubMedCrossRefGoogle Scholar
  48. Kaartinen V, Warburton D (2003) Fibrillin controls TGF-beta activation. Nat Genet 33:331–332PubMedCrossRefGoogle Scholar
  49. Kadoya K, Sasaki T, Kostka G, Timpl R, Matsuzaki K, Kumagai N, Sakai LY, Nishiyama T, Amano S (2005) Fibulin-5 deposition in human skin: decrease with ageing and ultraviolet B exposure and increase in solar elastosis. Br J Dermatol 153:607–612PubMedCrossRefGoogle Scholar
  50. Karu T (1999) Primary and secondary mechanisms of action of visible to near-IR radiation on cells. J Photochem Photobiol B Biol 49:1–17CrossRefGoogle Scholar
  51. Katayama K, Armendarizborunda J, Raghow R, Kang AH, Seyer JM (1993) A pentapeptide from type-I procollagen promotes extracellular-matrix production. J Biol Chem 268:9941–9944PubMedGoogle Scholar
  52. Kielty CM, Sherratt MJ, Shuttleworth CA (2002) Elastic fibres. J Cell Sci 115:2817–2828PubMedGoogle Scholar
  53. Kinsey R, Williamson MR, Chaudhry S, Mellody KT, McGovern A, Takahashi S, Shuttleworth CA, Kielty CM (2008) Fibrillin-1 microfibril deposition is dependent on fibronectin assembly. J Cell Sci 121:2696–2704PubMedCrossRefGoogle Scholar
  54. Kirschner R, Hubmacher D, Iyengar G, Kaur J, Fagotto-Kaufmann C, Bromme D, Bartels R, Reinhardt DP (2011) Classical and neonatal marfan syndrome mutations in fibrillin-1 cause differential protease susceptibilities and protein function. J Biol Chem 286:32810–32823PubMedPubMedCentralCrossRefGoogle Scholar
  55. Kligman AM, Grove GL, Hirose R, Leyden JJ (1986) Tpocial tretinoin for photoaged skin. J Am Acad Dermatol 15:836–859PubMedCrossRefGoogle Scholar
  56. Knuutinen A, Kallioinen M, Vahakangas K, Oikarinen A (2002) Smoking and skin: a study of the physical qualities and histology of skin in smokers and non-smokers. Acta Dermato-Venereol 82:36–40CrossRefGoogle Scholar
  57. Krutmann J (2003) Premature skin aging by ultraviolet radiation and other environmental hazards. The molecular basis. Hautarzt 54:809–817Google Scholar
  58. Langton AK, Sherratt MJ, Griffiths CEM, Watson REB (2012) Differential expression of elastic fibre components in intrinsically aged skin. Biogerontology 13:37–48PubMedCrossRefGoogle Scholar
  59. Lee P, Bax DV, Bilek MMM, Weiss AS (2014) A novel cell adhesion region in tropoelastin mediates attachment to integrin alpha(V)beta(5). J Biol Chem 289:1467–1477PubMedCrossRefGoogle Scholar
  60. Leyden JJ, Grove GL, Grove MJ, Thorne EG, Lufrano L (1989) Treatment of photodamaged facial skin with topical tretinoin. J Am Acad Dermatol 21:638–644PubMedCrossRefGoogle Scholar
  61. Li W, Fan J, Chen M, Guan S, Sawcer D, Bokoch GM, Woodley DT (2004) Mechanism of human dermal fibroblast migration driven by type I collagen and platelet-derived growth factor-BB. Mol Biol Cell 15:294–309PubMedPubMedCentralCrossRefGoogle Scholar
  62. Lin JY, Selim MA, Shea CR, Grichnik JM, Omar MM, Monteiro-Riviere NA, Pinnell SR (2003) UV photoprotection by combination topical antioxidants vitamin C and vitamin E. J Am Acad Dermatol 48:866–874PubMedCrossRefGoogle Scholar
  63. Lintner K, Peschard O (2000) Biologically active peptides: from a laboratory bench curiosity to a functional skin care product. Int J Cosmet Sci 22:207–218PubMedCrossRefGoogle Scholar
  64. Liu XQ, Zhao Y, Gao JG, Pawlyk B, Starcher B, Spencer JA, Yanagisawa H, Zuo J, Li TS (2004) Elastic fiber homeostasis requires lysyl oxidase-like 1 protein. Nat Genet 36:178–182PubMedCrossRefGoogle Scholar
  65. Loffek S, Hurskainen T, Jackow J, Sigloch FC, Schilling O, Tasanen K, Bruckner-Tuderman L, Franzke CW (2014) Transmembrane collagen XVII modulates integrin dependent keratinocyte migration via PI3K/Rac1 signaling. Plos One 9:11CrossRefGoogle Scholar
  66. Lopez-Torres M, Thiele JJ, Shindo Y, Han D, Packer L (1998) Topical application of alpha-tocopherol modulates the antioxidant network and diminishes ultraviolet-induced oxidative damage in murine skin. Br J Dermatol 138:207–215PubMedCrossRefGoogle Scholar
  67. Lucero HA, Kagan HM (2006) Lysyl oxidase: an oxidative enzyme and effector of cell function. Cell Mol Life Sci 63:2304–2316PubMedCrossRefGoogle Scholar
  68. Ma H, Wallis LK, Diamond S, Li S, Canas-Carrell J, Parra A (2014) Impact of solar UV radiation on toxicity of ZnO nanoparticles through photocatalytic reactive oxygen species (ROS) generation and photo-induced dissolution. Environ Pollut 193:165–172PubMedCrossRefGoogle Scholar
  69. Maia Campos PMBG, Goncalves GMS, Gaspar LR (2008) In vitro antioxidant activity and in vivo efficacy of topical formulations containing vitamin C and its derivatives studied by non-invasive methods. Skin Res Technol 14:376–380CrossRefGoogle Scholar
  70. Manova E, von Goetz N, Hungerbuhler K (2014) Ultraviolet filter contact and photocontact allergy: consumer exposure and risk assessment for octocrylene from personal care products and sunscreens. Br J Dermatol 171:1368–1374PubMedCrossRefGoogle Scholar
  71. Maquart FX, Monboisse JC (2014) Extracellular matrix and wound healing. Pathol Biol 62:91–95PubMedCrossRefGoogle Scholar
  72. Maquart FX, Pickart L, Laurent M, Gillery P, Monboisse JC, Borel JP (1988) Stimulation of collagen-synthesis in fibroblast-cultures by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-L-lysine-Cu2+. Febs Lett 238:343–346PubMedCrossRefGoogle Scholar
  73. Maquart FX, Bellon G, Chaqour B, Wegrowski J, Patt LM, Trachy RE, Monboisse JC, Chastang F, Birembaut P, Gillery P et al (1993) In-vivo stimulation of connective-tissue accumulation by the tripeptide copper complex glycyl-L-histidyl-L-lysine-Cu2+ in rat experimental wounds. J Clin Invest 92:2368–2376PubMedPubMedCentralCrossRefGoogle Scholar
  74. Marastoni S, Ligresti G, Lorenzon E, Colombatti A, Mongiat M (2008) Extracellular matrix: a matter of life and death. Connect Tissue Res 49:203–206PubMedCrossRefGoogle Scholar
  75. Marrot L, Belaidi JP, Lejeune F, Meunier JR, Asselineau D, Bernerd F (2004) Photostability of sunscreen products influences the efficiency of protection with regard to UV-induced genotoxic or photoageing-related endpoints. Br J Dermatol 151:1234–1244PubMedCrossRefGoogle Scholar
  76. Maruhashi T, Kii I, Saito M, Kudo A (2010) Interaction between periostin and BMP-1 promotes proteolytic activation of lysyl oxidase. J Biol Chem 285:13294–13303PubMedPubMedCentralCrossRefGoogle Scholar
  77. Massam-Wu T, Chiu M, Choudhury R, Chaudhry SS, Baldwin AK, McGovern A, Baldock C, Shuttleworth CA, Kielty CM (2010) Assembly of fibrillin microfibrils governs extracellular deposition of latent TGF beta. J Cell Sci 123:3006–3018PubMedPubMedCentralCrossRefGoogle Scholar
  78. Mellody KT, Freeman LJ, Baldock C, Jowitt TA, Siegler V, Raynal BDE, Cain SA, Wess TJ, Shuttleworth CA, Kielty CM (2006) Marfan syndrome-causing mutations in fibrillin-1 result in gross morphological alterations and highlight the structural importance of the second hybrid domain. J Biol Chem 281:31854–31862CrossRefPubMedGoogle Scholar
  79. Mienaltowski MJ, Birk DE (2014) Structure, physiology, and biochemistry of collagens. In: Halper J (ed) Progress in heritable soft connective tissue diseases, vol 802. Springer, Berlin, pp 5–29Google Scholar
  80. Murad S, Grove D, Lindberg KA, Reynolds G, Sivarajah A, Pinnell SR (1981) Regulation of collagen synthesis by ascorbic acid. Proc Natl Acad Sci USA Biol Sci 78:2879–2882CrossRefGoogle Scholar
  81. Muta-Takada K, Terada T, Yamanishi H, Ashida Y, Inomata S, Nishiyama T, Amano S (2009) Coenzyme Q(10) protects against oxidative stress-induced cell death and enhances the synthesis of basement membrane components in dermal and epidermal cells. Biofactors 35:435–441PubMedCrossRefGoogle Scholar
  82. Naylor EC, Watson REB, Sherratt MJ (2011) Molecular aspects of skin ageing. Maturitas 69:249–256PubMedCrossRefGoogle Scholar
  83. Neptune ER, Frischmeyer PA, Arking DE, Myers L, Bunton TE, Gayraud B, Ramirez F, Sakai LY, Dietz HC (2003) Dysregulation of TGF-beta activation contributes to pathogenesis in Marfan syndrome. Nat Genet 33:407–411PubMedCrossRefGoogle Scholar
  84. Nusgens BV, Humbert P, Rougier A, Colige AC, Haftek M, Lambert CA, Richard A, Creidi P, Lapiere CM (2001) Topically applied vitamin C enhances the mRNA level of collagens I and III, their processing enzymes and tissue inhibitor of matrix metalloproteinase 1 in the human dermis. J Invest Dermatol 116:853–859PubMedCrossRefGoogle Scholar
  85. O’Hare PM, Fleischer AB, D’Agostino RB, Feldman SR, Hinds MA, Rassette SA, McMichael AJ, Williford PM (1999) Tobacco smoking contributes little to facial wrinkling. J Eur Acad Dermatol Venereol 12:133–139PubMedCrossRefGoogle Scholar
  86. Okano Y, Obayashi K, Yahagi S, Kurihara K, Kaburagi S, Kurata Y, Masaki H (2006) Improvement of wrinkles by an all-trans-retinoic acid derivative, D-delta-tocopheryl retinoate. J Dermatol Sci: S65–S74Google Scholar
  87. Papakonstantinou E, Roth M, Karakiulakis G (2012) Hyaluronic acid: a key molecule in skin aging. Dermatoendocrinol 4:253–258PubMedPubMedCentralCrossRefGoogle Scholar
  88. Pattison D, Rahmanto A, Davies M (2011) Photo-oxidation of proteins. Photochem Photobiol Sci 11:38–53PubMedCrossRefGoogle Scholar
  89. Ramirez F, Sakai LY (2010) Biogenesis and function of fibrillin assemblies. Cell Tissue Res 339:71–82PubMedCrossRefGoogle Scholar
  90. Ramshaw JAM, Shah NK, Brodsky B (1998) Gly-X-Y tripeptide frequencies in collagen: a context for host-guest triple-helical peptides. J Struct Biol 122:86–91PubMedCrossRefGoogle Scholar
  91. Raschke T, Koop U, Dusing HJ, Filbry A, Sauermann K, Jaspers S, Wenck H, Wittern KP (2004) Topical activity of ascorbic acid: from in vitro optimization to in vivo efficacy. Skin Pharmacol Physiol 17:200–206PubMedCrossRefGoogle Scholar
  92. Robinson LR, Fitzgerald NC, Doughty DG, Dawes NC, Berge CA, Bissett DL (2005) Topical palmitoyl pentapeptide provides improvement in photoaged human facial skin. Int J Cosmet Sci 27:155–160PubMedCrossRefGoogle Scholar
  93. Rosado JP, Favorito LA, Cavalcanti AGL, Costa WS, Cardoso LEM, Sampaio FJB (2012) Structural alterations of foreskin caused by chronic smoking may explain high levels of urethral reconstruction failure using foreskin flaps. Int Braz J Urol 38:529–535 Google Scholar
  94. Ruehland C, Schonherr E, Robenek H, Hansen U, Iozz RV, Bruckner P, Seidler DG (2007) The glycosaminoglycan chain of decorin plays an important role in collagen fibril formation at the early stages of fibrillogenesis. FEBS J 274:4246–4255CrossRefGoogle Scholar
  95. Sabatelli P, Gara SK, Grumati P, Urciuolo A, Gualandi F, Curci R, Squarzoni S, Zamparelli A, Martoni E, Merlini L et al (2011) Expression of the collagen VI alpha 5 and alpha 6 chains in normal human skin and in skin of patients with collagen VI-related myopathies. J Invest Dermatol 131:99–107PubMedCrossRefGoogle Scholar
  96. Sabatier L, Djokic J, Hubmacher D, Dzafik D, Nelea V, Reinhardt DP (2014) Heparin/heparan sulfate controls fibrillin-1, -2 and -3 self-interactions in microfibril assembly. Febs Lett 588:2890–2897PubMedCrossRefGoogle Scholar
  97. Sakai LY, Keene DR, Engvall E (1986) Fibrillin, a new 350-kD glycoprotein, is a component of extracellular microfibrils. J Cell Biol 103:2499–2509PubMedCrossRefGoogle Scholar
  98. Sander CS, Chang H, Salzmann S, Muller CSL, Ekanayake-Mudiyanselage S, Elsner P, Thiele JJ (2002) Photoaging is associated with protein oxidation in human skin in vivo. J Invest Dermatol 118:618–625PubMedCrossRefGoogle Scholar
  99. Schieke SM, Stege H, Kurten V, Grether-Beck S, Sies H, Krutmann J (2002) Infrared-A radiation-induced matrix metalloproteinase 1 expression is mediated through extracellular signal-regulated kinase 1/2 activation in human dermal fibroblasts. J Invest Dermatol 119:1323–1329PubMedCrossRefGoogle Scholar
  100. Schieke SM, Schroeder P, Krutmann J (2003) Cutaneous effects of infrared radiation: from clinical observations to molecular response mechanisms. Photodermatol Photoimmunol Photomed 19:228–234PubMedCrossRefGoogle Scholar
  101. Sellheyer K (2003) Pathogenesis of solar elastosis: synthesis or degradation? J Cutan Pathol 30:123–127PubMedCrossRefGoogle Scholar
  102. Sherratt MJ (2015) Body mass index and dermal remodelling. Exp DermatolGoogle Scholar
  103. Sherratt MJ, Bayley CP, Reilly SM, Gibbs NK, Griffiths CEM, Watson REB (2010) Low-dose ultraviolet radiation selectively degrades chromophore-rich extracellular matrix components. J Pathol 222:32–40PubMedGoogle Scholar
  104. Shibata T, Sakai N, Fukuda K, Ebina Y, Sasaki T (2007) Photocatalytic properties of titania nanostructured films fabricated from titania nanosheets. Phys Chem Chem Phys 9:2413–2420PubMedCrossRefGoogle Scholar
  105. Skovgaard GRL, Jensen AS, Sigler ML (2006) Effect of a novel dietary supplement on skin aging in post-menopausal women. Eur J Clin Nutr 60:1201–1206PubMedCrossRefGoogle Scholar
  106. Stuart K, Paderi J, Snyder PW, Freeman L, Panitch A (2011) Collagen-binding peptidoglycans inhibit MMP mediated collagen degradation and reduce dermal scarring. Plos One 6:7CrossRefGoogle Scholar
  107. Talwar HS, Griffiths CEM, Fisher GJ, Hamilton TA, Voorhees JJ (1995) Reduced type-I and type-III procollagens in photodamaged adult human skin. J Invest Dermatol 105:285–290PubMedCrossRefGoogle Scholar
  108. Theocharidis G, Drymoussi Z, Kao AP, Barber AH, Lee DA, Braun KM, Connelly JT (2015) Type VI collagen regulates dermal matrix assembly and fibroblast motility. J Invest DermatolGoogle Scholar
  109. Tiecke F, Katzke S, Booms P, Robinson PN, Neumann L, Godfrey M, Mathews KR, Scheuner M, Hinkel GK, Brenner RE et al (2001) Classic, atypically severe and neonatal Marfan syndrome: twelve mutations and genotype-phenotype correlations in FBN1 exons 24-40. Eur J Hum Genet 9:13–21PubMedCrossRefGoogle Scholar
  110. Tovar-Sanchez A, Sanchez-Quiles D, Basterretxea G, Benede JL, Chisvert A, Salvador A, Moreno-Garrido I, Blasco J (2013) Sunscreen products as emerging pollutants to coastal waters. Plos One 8:8CrossRefGoogle Scholar
  111. Tran DT, Salmon R (2011) Potential photocarcinogenic effects of nanoparticle sunscreens. Australas J Dermatol 52:1–6PubMedCrossRefGoogle Scholar
  112. Uitto J (2008) The role of elastin and collagen in cutaneous aging: intrinsic aging versus photoexposure. J Drugs Dermatol JDD 7:s12–s16PubMedGoogle Scholar
  113. Wang F, Garza LA, Kang S, Varani J, Orringer JS, Fisher GJ, Voorhees JJ (2007) In vivo stimulation of de novo collagen production caused by cross-linked hyaluronic acid dermal filler injections in photodamaged human skin. Arch Dermatol 143:155–163PubMedGoogle Scholar
  114. Warren R, Gartstein V, Kligman AM, Montagna W, Allendorf RA, Ridder GM (1991) Age, sunlight, and facial skin: a histologic and quantitative study. J Am Acad Dermatol 25:751–760PubMedCrossRefGoogle Scholar
  115. Warskulat U, Reinen A, Grether-Beck S, Krutmann J, Haussinger D (2004) The osmolyte strategy of normal human keratinocytes in maintaining cell homeostasis. J Invest Dermatol 123:516–521PubMedCrossRefGoogle Scholar
  116. Watson REB, Griffiths CEM, Craven NM, Shuttleworth CA, Kielty CM (1999) Fibrillin-rich microfibrils are reduced in photoaged skin. Distribution at the dermal-epidermal junction. J Invest Dermatol 112:782–787PubMedCrossRefGoogle Scholar
  117. Watson REB, Craven NM, Kang SW, Jones CJP, Kielty CM, Griffiths CEM (2001) A short-term screening protocol, using fibrillin-1 as a reporter molecule, for photoaging repair agents. J Invest Dermatol 116:672–678PubMedCrossRefGoogle Scholar
  118. Watson REB, Long SP, Bowden JJ, Bastrilles JY, Barton SP, Griffiths CEM (2008) Repair of photoaged dermal matrix by topical application of a cosmetic ‘antiageing’ product. Br J Dermatol 158:472–477PubMedCrossRefGoogle Scholar
  119. Watson REB, Ogden S, Cotterell LF, Bowden JJ, Bastrilles JY, Long SP, Griffiths CEM (2009) A cosmetic ‘anti-ageing’ product improves photoaged skin: a double-blind, randomized controlled trial. Br J Dermatol 161:419–426PubMedPubMedCentralCrossRefGoogle Scholar
  120. Watson REB, Gibbs NK, Griffiths CEM, Sherratt MJ (2014) Damage to skin extracellular matrix induced by UV exposure. Antioxid Redox Signal 21:1063–1077PubMedCrossRefGoogle Scholar
  121. Wondrak GT (2007) Let the sun shine in: mechanisms and potential for therapeutics in skin photodamage. Curr Opin Invest Drugs 8:390–400Google Scholar
  122. Wondrak GT, Roberts MJ, Cervantes-Laurean D, Jacobson MK, Jacobson EL (2003) Proteins of the extracellular matrix are sensitizers of photo-oxidative stress in human skin cells. J Invest Dermatol 121:578–586PubMedCrossRefGoogle Scholar
  123. Wondrak GT, Jacobson MK, Jacobson EL (2006) Endogenous UVA-photosensitizers: mediators of skin photodamage and novel targets for skin photoprotection. Photochem Photobiol Sci 5:215–237PubMedCrossRefGoogle Scholar
  124. Woodley DT, Zelickson AS, Briggaman RA, Hamilton TA, Weiss JS, Ellis CN, Voorhees JJ (1990) Treatment of photoaged skin with topical tretinoin increases epidermal-dermal anchoring fibrils—a preliminary report. Jama J Am Med Assoc 263:3057–3059CrossRefGoogle Scholar
  125. Xiao JH, Durand B, Chambon P, Voorhees JJ (1995) Endogenous retinoic acid receptor (RAR)-retinoid X receptor (RXR) heterodimers are the major functional forms regulating retinoid-responsive elements in adult human keratinocytes. Binding of ligands to RAR only is sufficient for RAR-RXR heterodimers to confer ligand-dependent activation of hRAR beta 2/RARE (DR5). J Biol Chem 270:3001–3011PubMedCrossRefGoogle Scholar
  126. Yaar M, Gilchrest BA (2007) Photoageing: mechanism, prevention and therapy. British J Dermatol 157:874–887CrossRefGoogle Scholar
  127. Yamaguchi Y, Mann DM, Ruoslahti E (1990) Negative regulation of transforming growth-factor-beta by the proteoglycan decorin. Nature 346:281–284PubMedCrossRefGoogle Scholar
  128. Young AR (1997) Chromophores in human skin. Phys Med Biol 42:789–802PubMedCrossRefGoogle Scholar
  129. Zatterstrom UK, Felbor U, Fukai N, Olsen BR (2000) Collagen XVIII/endostatin structure and functional role in angiogenesis. Cell Struct Funct 25:97–101PubMedCrossRefGoogle Scholar
  130. Zhang G, Chen S, Goldoni S, Calder BW, Simpson HC, Owens RT, McQuillan DJ, Young MF, Iozzo RV, Birk DE (2009) Genetic evidence for the coordinated regulation of collagen fibrillogenesis in the cornea by decorin and biglycan. J Biol Chem 284:8888–8897PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Centre for Tissue Injury and Repair, Institute of Inflammation and RepairThe University of ManchesterManchesterUK
  2. 2.Walgreens Boots AllianceNottinghamUK

Personalised recommendations