Cutaneous Oxidative Stress and Aging

  • Thomas G. Polefka
  • Thomas A. Meyer
Living reference work entry


The earliest known microfossil records suggest that microorganisms existed on the earth approximately 3.8 billion years ago. With the aid of sunlight, these photosynthetic organisms began to generate molecular oxygen (O2) and fundamentally changed the earth’s atmosphere and direction of evolution. Paradoxically, an atmosphere of ~20 % oxygen offers aerobic organisms both benefits and challenges. As the outermost boundary, the skin is continuously exposed to various environmental stresses ranging from O2 itself to solar radiation, air pollution, and lifestyle excesses, all of which can produce oxidative stress. This chapter summarizes almost 60 years of research and provides a “60,000 ft” perspective on cutaneous oxidative stress. Topics reviewed include: What are free radicals and reactive oxidizing species (ROS)? Where do they come from and how are they formed? What is their chemistry and molecular targets? What are their roles in health and disease in general and the skin in particular? How does the skin protect itself from these reactive species? And finally, what roles do ROS and oxidative stress play in the aging process?


Stratum Corneum Antioxidant Defense System Skin Aging Reactive Oxidize Species Nicotinamide Adenine Dinucleotide Phosphate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Des Marais DJ. When did photosynthesis emerge on earth? Science. 2000;289(5485):1703–5.Google Scholar
  2. 2.
    Falkowski PG, Godfrey LV. Electrons, life and the evolution of Earth’s oxygen cycle. Philos Trans R Soc Lond B Biol Sci. 2008;363(1504):2705–16.PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Graham JB, Aguilar NM, Dudley R, Gans C. Implications of the late Palaeozoic oxygen pulse for physiology and evolution. Nature. 1995;375(6527):117–20.CrossRefGoogle Scholar
  4. 4.
    Wright CJ, Dennery PA. Manipulation of gene expression by oxygen: a primer from bedside to bench. Pediatr Res. 2009;66(1):3–10.PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Maltepe E, Saugstad OD. Oxygen in health and disease: regulation of oxygen homeostasis – clinical implications. Pediatr Res. 2009;65(3):261–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Auten RL, Davis JM. Oxygen toxicity and reactive species: the devil is in the details. Pediatr Res. 2009;66(2):121–7.PubMedCrossRefGoogle Scholar
  7. 7.
    Voet D, Voet JG. Biochemistry. 4th ed. New York: Wiley; 2010.Google Scholar
  8. 8.
    Halliwell B. Reactive species and antioxidants. Redox biology is a fundamental theme of aerobic life. Plant Physiol. 2006;141(2):312.PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Halliwell B, Gutteridge J. Free radicals in biology and medicine. 4th ed. Oxford/New York: Oxford University Press; 2007.Google Scholar
  10. 10.
    Kalyanaraman B. Teaching the basics of redox biology to medical and graduate students: oxidants, antioxidants and disease mechanisms. Redox Biol. 2013;1(1):244–57.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Cadet J, Douki T, Ravanat J-L. Oxidatively generated damage to cellular DNA by UVB and UVA radiation. Photochem Photobiol. 2015;91(1):140–55.PubMedCrossRefGoogle Scholar
  12. 12.
    Davies MJ. The oxidative environment and protein damage. Biochim Biophys Acta. 2005;1703(2):93–109.PubMedCrossRefGoogle Scholar
  13. 13.
    Peres PS, Terra VA, Guarnier FA, Cecchini R, Cecchini AL. Photoaging and chronological aging profile: understanding oxidation of the skin. J Photochem Photobiol B Biol. 2011;103(2):93–7.CrossRefGoogle Scholar
  14. 14.
    McCord JM. The evolution of free radicals and oxidative stress. Am J Med. 2000;108(8):652–9.PubMedCrossRefGoogle Scholar
  15. 15.
    Sies H. Strategies of antioxidant defense. Euro J Biochem. 1993;215(2):213–9.CrossRefGoogle Scholar
  16. 16.
    Stoyanovsky DA, Maeda A, Atkins JL, Kagan VE. Assessments of thiyl radicals in biosystems: difficulties and new applications. Anal Chem. 2011;83(17):6432–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Wölfle U, Seelinger G, Bauer G, Meinke MC, Lademann J, Schempp CM. Reactive molecule species and antioxidative mechanisms in normal skin and skin aging. Skin Pharmacol Physiol. 2014;27(6):316–32.PubMedCrossRefGoogle Scholar
  18. 18.
    Marinho HS, Real C, Cyrne L, Soares H, Antunes F. Hydrogen peroxide sensing, signaling and regulation of transcription factors. Redox Biol. 2014;2:535–62.PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Buettner GR. The pecking order of free radicals and antioxidants: lipid peroxidation, alpha-tocopherol, and ascorbate. Arch Biochem Biophys. 1993;300(2):535–43.PubMedCrossRefGoogle Scholar
  20. 20.
    Finkel T, Holbrook NJ. Oxidants, oxidative stress and the biology of ageing. Nature. 2000;408(6809):239–47.PubMedCrossRefGoogle Scholar
  21. 21.
    Petibois C, Gionnet K, Goncalves M, Perromat A, Moenner M, Deleris G. Analytical performances of FT-IR spectrometry and imaging for concentration measurements within biological fluids, cells, and tissues. Analyst. 2006;131(5):640.PubMedCrossRefGoogle Scholar
  22. 22.
    Leung TH, Zhang LF, Wang J, Ning S, Knox SJ, Kim SK. Topical hypochlorite ameliorates NF-κB–mediated skin diseases in mice. J Clin Invest. 2013;123(12):5361–70.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Radi R. Peroxynitrite, a stealthy biological oxidant. J Biol Chem. 2013;288(37):26464–72.PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Wondrak GT, Jacobson MK, Jacobson EL. Endogenous UVA-photosensitizers: mediators of skin photodamage and novel targets for skin photoprotection. Photochem Photobiol Sci. 2006;5(2):215–37.PubMedCrossRefGoogle Scholar
  25. 25.
    Ogilby PR. Singlet oxygen: there is still something new under the sun, and it is better than ever. Photochem Photobiol Sci. 2010;9(12):1543–60.PubMedCrossRefGoogle Scholar
  26. 26.
    Circu ML, Aw TY. Reactive oxygen species, cellular redox systems, and apoptosis. Free Radic Biol Med. 2010;48(6):749–62.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    del Río LA. Peroxisomes as a cellular source of reactive nitrogen species signal molecules. Arch Biochem Biophys. 2011;506(1):1–11.PubMedCrossRefGoogle Scholar
  28. 28.
    Sena L, Chandel N. Physiological roles of mitochondrial reactive species. Mol Cell. 2012;48(2):158–67.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Giorgio M, Trinei M, Migliaccio E, Pelicci PG. Hydrogen peroxide: a metabolic by-product or a common mediator of ageing signals? Nat Rev Mol Cell Biol. 2007;8(9):722–8.PubMedCrossRefGoogle Scholar
  30. 30.
    Hill BG, Dranka BP, Bailey SM, Lancaster Jr JR, Darley-Usmar VM. What part of NO don’t you understand? Some answers to the cardinal questions in nitric oxide biology. J Biol Chem. 2010;285(26):19699–704.PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Freinbichler W, Colivicchi MA, Stefanini C, Bianchi L, Ballini C, Misini B, et al. Highly reactive species: detection, formation, and possible functions. Cell Mol Life Sci. 2011;68(12):2067–79.PubMedCrossRefGoogle Scholar
  32. 32.
    Nathan C, Cunningham-Bussel A. Beyond oxidative stress: an immunologist’s guide to reactive species. Nat Rev Immunol. 2013;13(5):349–61.PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Ryan JL. Ionizing radiation: the good, the bad, and the ugly. J Invest Dermatol. 2012;132:985–93.PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Polefka TG, Meyer TA, Agin PP, Bianchini RJ. Effects of solar radiation on the skin. J Cosmet Dermatol. 2012;11(2):134–43.PubMedCrossRefGoogle Scholar
  35. 35.
    Krutmann J, Liu W, Li L, Pan X, Crawford M, Sore G, et al. Pollution and skin: from epidemiological and mechanistic studies to clinical implications. J Dermatol Sci. 2014;76(3):163–8.PubMedCrossRefGoogle Scholar
  36. 36.
    Kovacic P, Somanathan R. Dermal toxicity and environmental contamination: electron transfer, reactive species, oxidative stress, cell signaling, and protection by antioxidants. Rev Environ Contam Toxicol. 2010;203:119–38.PubMedGoogle Scholar
  37. 37.
    Fang YZ, Yang S, Wu G. Free radicals, antioxidants, and nutrition. Nutrition. 2002;18(10):872–9.PubMedCrossRefGoogle Scholar
  38. 38.
    Cadenas E, Davies KJ. Mitochondrial free radical generation, oxidative stress, and aging. Free Radic Biol Med. 2000;29(3–4):222–30.PubMedCrossRefGoogle Scholar
  39. 39.
    Alfadda AA, Sallam RM. Reactive oxygen species in health and disease. J Biomed Biotechnol. 2012;2012:936486.PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Ray PD, Huang B-W, Tsuji Y. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal. 2012;24(5):981–90.PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Droge W. Free radicals in the physiological control of cell function. Physiol Rev. 2002;82(1):47–95.PubMedCrossRefGoogle Scholar
  42. 42.
    Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol. 2007;39(1):44–84.PubMedCrossRefGoogle Scholar
  43. 43.
    Fitzmaurice SD, Sivamani RK, Isseroff RR. Antioxidant therapies for wound healing: a clinical guide to currently commercially available products. Skin Pharmacol Physiol. 2011;24(3):113–26.PubMedCrossRefGoogle Scholar
  44. 44.
    Grether-Beck S, Marini A, Jaenicke T, Krutmann J. Photoprotection of human skin beyond ultraviolet radiation. Photodermatol Photoimmunol Photomed. 2014;30(2–3):167–74.PubMedCrossRefGoogle Scholar
  45. 45.
    Park SL, Justiniano R, Williams JD, Cabello CM, Qiao S, Wondrak GT. The tryptophan-derived endogenous aryl hydrocarbon receptor ligand 6-formylindolo[3,2-b]carbazole is a nanomolar UVA photosensitizer in epidermal keratinocytes. J Invest Dermatol. 2015;135:1649–58.PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Chiarelli-Neto O, Ferreira AS, Martins WK, Pavani C, Severino D, Faiao-Flores F, et al. Melanin photosensitization and the effect of visible light on epithelial cells. PLoS One. 2014;9(11):e113266.PubMedCentralPubMedCrossRefGoogle Scholar
  47. 47.
    Dawe RS, Ibbotson SH. Drug-induced photosensitivity. Dermatol Clin. 2014;32(3):363–8.PubMedCrossRefGoogle Scholar
  48. 48.
    Buettner GR. Superoxide dismutase in redox biology: the roles of superoxide and hydrogen peroxide. Anticancer Agents Med Chem. 2011;11(4):341–6.PubMedCentralPubMedCrossRefGoogle Scholar
  49. 49.
    Sies H. Oxidative stress: from basic research to clinical application. Am J Med. 1991;91(3c):31–8.CrossRefGoogle Scholar
  50. 50.
    Bissett DL, Chatterjee R, Hannon DP. Chronic ultraviolet radiation-induced increase in skin iron and the photoprotective effect of topically applied iron chelators. Photochem Photobiol. 1991;54(2):215–23.PubMedCrossRefGoogle Scholar
  51. 51.
    Bissett DL, McBride JF. Iron content of human epidermis from sun-exposed and non-exposed body sites. J Soc Cosmet Chem. 1992;43:215–7.Google Scholar
  52. 52.
    Bissett DL, McBride JF. Synergistic topical photoprotection by a combination of the iron chelator 2-furildioxime and sunscreen. J Am Acad Dermatol. 1996;35(4):546–9.PubMedCrossRefGoogle Scholar
  53. 53.
    Aroun A, Zhong JL, Tyrrell RM, Pourzand C. Iron, oxidative stress and the example of solar ultraviolet A radiation. Photochem Photobiol Sci. 2012;11(1):118–34.PubMedCrossRefGoogle Scholar
  54. 54.
    Jomova K, Baros S, Valko M. Redox active metal-induced oxidative stress in biological systems. Transit Met Chem. 2012;37(2):127–34.CrossRefGoogle Scholar
  55. 55.
    Valacchi G, Sticozzi C, Pecorelli A, Cervellati F, Cervellati C, Maioli E. Cutaneous responses to environmental stressors. Ann NY Acad Sci. 2012;1271(1):75–81.PubMedCentralPubMedCrossRefGoogle Scholar
  56. 56.
    Poljsak B, Dahmane R. Free radicals and extrinsic skin aging. Dermatol Res Pract. 2012;4. doi:10.1155/2012/135206.Google Scholar
  57. 57.
    Bickers DR, Athar M. Oxidative stress in the pathogenesis of skin disease. J Invest Dermatol. 2006;126(12):2565–75.PubMedCrossRefGoogle Scholar
  58. 58.
    Starr JM, Starr RJ. Skin aging and oxidative stress, Chapter 2. In: Preedy VR, editor. Aging: Oxidative Stress and Dietary Antioxidants. Oxford, UK, and Waltham, MA, USA, Academic Press; 2014. p. 15–22.Google Scholar
  59. 59.
    Kammeyer A, Luiten RM. Oxidation events and skin aging. Ageing Res Rev. 2015;21:16–29.PubMedCrossRefGoogle Scholar
  60. 60.
    Kryston TB, Georgiev AB, Pissis P, Georgakilas AG. Role of oxidative stress and DNA damage in human carcinogenesis. Mutat Res. 2011;711(1–2):193–201.PubMedCrossRefGoogle Scholar
  61. 61.
    Jena NR. DNA damage by reactive species: mechanisms, mutation and repair. J Biosci. 2012;37(3):503–17.PubMedCrossRefGoogle Scholar
  62. 62.
    Pfeifer GP, Besaratinia A. UV wavelength-dependent DNA damage and human non-melanoma and melanoma skin cancer. Photochem Photobiol Sci. 2012;11(1):90–7.PubMedCentralPubMedCrossRefGoogle Scholar
  63. 63.
    van Loon B, Markkanen E, Hübscher U. Oxygen as a friend and enemy: how to combat the mutational potential of 8-oxo-guanine. DNA Repair. 2010;9(6):604–16.PubMedCrossRefGoogle Scholar
  64. 64.
    Rastogi RP, Richa, Kumar A, Tyagi MB, Sinha RP. Molecular mechanisms of ultraviolet radiation-induced DNA damage and repair. J Nucleic Acids. 2010;32. doi:10.4061/2010/592980.Google Scholar
  65. 65.
    Brash DE. UV signature mutations. Photochem Photobiol. 2015;91(1):15–26.PubMedCrossRefPubMedCentralGoogle Scholar
  66. 66.
    Boukamp P. Non-melanoma skin cancer: what drives tumor development and progression? Carcinogenesis. 2005;26(10):1657–67.PubMedCrossRefGoogle Scholar
  67. 67.
    Chial H. Proto-oncogenes to oncogenes to cancer. Nat Educ. 2008;1(1):33.Google Scholar
  68. 68.
    Marrot L, Meunier JR. Skin DNA photodamage and its biological consequences. J Am Acad Dermatol. 2008;58(5):S139–48.PubMedCrossRefGoogle Scholar
  69. 69.
    Premi S, Wallisch S, Mano CM, Weiner AB, Bacchiocchi A, Wakamatsu K, et al. Chemiexcitation of melanin derivatives induces DNA photoproducts long after UV exposure. Science. 2015;347(6224):842–7.PubMedCentralPubMedCrossRefGoogle Scholar
  70. 70.
    Taylor J-S. The dark side of sunlight and melanoma. Science. 2015;347(6224):824.PubMedCrossRefGoogle Scholar
  71. 71.
    Murphy MP. How mitochondria produce reactive species. Biochem J. 2009;417(Pt 1):1–13.PubMedCentralPubMedCrossRefGoogle Scholar
  72. 72.
    Birch-Machin MA, Swalwell H. How mitochondria record the effects of UV exposure and oxidative stress using human skin as a model tissue. Mutagenesis. 2010;25(2):101–7.PubMedCrossRefGoogle Scholar
  73. 73.
    Grether-Beck S, Marini A, Jaenicke T, Krutmann J. Effective photoprotection of human skin against infrared A radiation by topically applied antioxidants: results from a vehicle controlled, randomized study. Photochem Photobiol. 2015;91(1):248–50.PubMedCrossRefGoogle Scholar
  74. 74.
    Wallace DC. Mitochondrial DNA, mutations in disease and aging. Environ Mol Mutagen. 2010;51(5):440–50.PubMedGoogle Scholar
  75. 75.
    Gredilla R, Bohr VA, Stevnsner T. Mitochondrial DNA repair and association with aging – an update. Exp Gerontol. 2010;45(7–8):478–88.Google Scholar
  76. 76.
    Birch-Machin MA, Russell EV, Latimer JA. Mitochondrial DNA damage as a biomarker for ultraviolet radiation exposure and oxidative stress. Br J Dermatol. 2013;169(Suppl S2):9–14.PubMedCrossRefGoogle Scholar
  77. 77.
    Gebhard D, Mahler B, Matt K, Burger K, Bergemann J. Mitochondrial DNA copy number – but not a mitochondrial tandem CC to TT transition – is increased in sun-exposed skin. Exp Dermatol. 2014;23(3):209–11.PubMedCrossRefGoogle Scholar
  78. 78.
    Birch-Machin MA. Mitochondria and skin disease. Clin Exp Dermatol. 2000;25(2):141–6.PubMedCrossRefGoogle Scholar
  79. 79.
    Niki E. Lipid oxidation in the skin. Free Rad Res. 2015;49(7):827-834.Google Scholar
  80. 80.
    Niki E, Yoshida Y, Saito Y, Noguchi N. Lipid peroxidation: mechanisms, inhibition, and biological effects. Biochem Biophys Res Commun. 2005;338(1):668–76.PubMedCrossRefGoogle Scholar
  81. 81.
    Valko M, Morris H, Cronin MT. Metals, toxicity and oxidative stress. Curr Med Chem. 2005;12(10):1161–208.PubMedCrossRefGoogle Scholar
  82. 82.
    Halliwell B, Chirico S. Lipid peroxidation: its mechanism, measurement, and significance. Am J Clin Nutr. 1993;57(Suppl):715S–25.PubMedGoogle Scholar
  83. 83.
    Kendall AC, Pilkington SM, Massey KA, Sassano G, Rhodes LE, Nicolaou A. Distribution of bioactive lipid mediators in human skin. J Invest Dermatol. 2015;135:1510–20.PubMedCrossRefGoogle Scholar
  84. 84.
    Nicolaou A. Eicosanoids in skin inflammation. Prostaglandins Leukot Essent Fatty Acids. 2013;88(1):131–8.PubMedCrossRefGoogle Scholar
  85. 85.
    Kendall AC, Nicolaou A. Bioactive lipid mediators in skin inflammation and immunity. Prog Lipid Res. 2013;52(1):141–64.PubMedCrossRefGoogle Scholar
  86. 86.
    Li Y, Lei D, Swindell WR, Xia W, Weng S, Fu J, et al. Age-associated increase in skin fibroblast-derived prostaglandin E2 contributes to reduced collagen levels in elderly human skin. J Invest Dermatol. 2015;135:2181–2188.Google Scholar
  87. 87.
    Franceschi C, Bonafe M, Valensin S, Olivieri F, De Luca M, Ottaviani E, et al. Inflamm-aging: an evolutionary perspective on immunosenescence. Ann NY Acad Sci. 2000;908(1):244–54.PubMedCrossRefGoogle Scholar
  88. 88.
    Cevenini E, Monti D, Franceschi C. Inflamm-ageing. Curr Opin Clin Nutr Metab Care. 2013;16(1):14–20.PubMedCrossRefGoogle Scholar
  89. 89.
    Cannizzo ES, Clement CC, Sahu R, Follo C, Santambrogio L. Oxidative stress, inflamm-aging and immunosenescence. J Proteomics. 2011;74(11):2313–23.PubMedCrossRefGoogle Scholar
  90. 90.
    Xu F, Yan S, Wu M, Li F, Xu X, Song W, et al. Ambient ozone pollution as a risk factor for skin disorders. Br J Dermatol. 2011;165(1):224–5.PubMedCrossRefGoogle Scholar
  91. 91.
    Avery SV. Molecular targets of oxidative stress. Biochem J. 2011;434(2):201–10.PubMedCrossRefGoogle Scholar
  92. 92.
    Thiele JJ, Dreher F, Maibach HI, Packer L. Impact of ultraviolet radiation and ozone on the transepidermal water loss as a function of skin temperature in hairless mice. Skin Pharmacol Appl Skin Physiol. 2003;16(5):283–90.PubMedCrossRefGoogle Scholar
  93. 93.
    Fritz KS, Petersen DR. An overview of the chemistry and biology of reactive aldehydes. Free Radic Biol Med. 2013;59:85–91.PubMedCentralPubMedCrossRefGoogle Scholar
  94. 94.
    Mudiyanselage SE, Hamburger M, Elsner P, Thiele JJ. Ultraviolet A induces generation of squalene monohydroperoxide isomers in human sebum and skin surface lipids in vitro and in vivo. J Invest Dermatol. 2003;120(6):915–22.CrossRefGoogle Scholar
  95. 95.
    Wisthaler A, Weschler CJ. Reactions of ozone with human skin lipids: sources of carbonyls, dicarbonyls, and hydroxycarbonyls in indoor air. Proc Natl Acad Sci U S A. 2010;107(15):6568–75.PubMedCentralPubMedCrossRefGoogle Scholar
  96. 96.
    De Luca C, Valacchi G. Surface lipids as multifunctional mediators of skin responses to environmental stimuli. Mediators Inflamm. 2010; doi:10.1155/2010/321494, 11 pg.Google Scholar
  97. 97.
    Dalle-Donne I, Rossi R, Colombo R, Giustarini D, Milzani A. Biomarkers of oxidative damage in human disease. Clin Chem. 2006;52(4):601–23.PubMedCrossRefGoogle Scholar
  98. 98.
    Stadtman ER. Protein oxidation and aging. Science. 1992;257(5074):1220–4.PubMedCrossRefGoogle Scholar
  99. 99.
    Stadtman ER. Metal ion-catalyzed oxidation of proteins: biochemical mechanism and biological consequences. Free Radic Biol Med. 1990;9(4):315–25.PubMedCrossRefGoogle Scholar
  100. 100.
    Stadtman ER, Berlett BS. Reactive oxygen-mediated protein oxidation in aging and disease. Chem Res Toxicol. 1997;10(5):485–94.PubMedCrossRefGoogle Scholar
  101. 101.
    Cecarini V, Gee J, Fioretti E, Amici M, Angeletti M, Eleuteri AM, et al. Protein oxidation and cellular homeostasis: emphasis on metabolism. Biochim Biophys Acta. 2007;1773(2):93–104.PubMedCrossRefGoogle Scholar
  102. 102.
    Jung T, Höhn A, Grune T. The proteasome and the degradation of oxidized proteins: part II – protein oxidation and proteasomal degradation. Redox Biol. 2014;2:99–104.PubMedCentralCrossRefGoogle Scholar
  103. 103.
    Moller IM, Rogowska-Wrzesinska A, Rao RS. Protein carbonylation and metal-catalyzed protein oxidation in a cellular perspective. J Proteomics. 2011;74(11):2228–42.PubMedCrossRefGoogle Scholar
  104. 104.
    Rudyk O, Eaton P. Biochemical methods for monitoring protein thiol redox states in biological systems. Redox Biol. 2014;2:803–13.PubMedCentralPubMedCrossRefGoogle Scholar
  105. 105.
    Go YM, Jones DP. The redox proteome. J Biol Chem. 2013;288(37):26512–20.PubMedCentralPubMedCrossRefGoogle Scholar
  106. 106.
    Manton C, Chandra J. Oxidative stress and the proteasome: mechanisms and therapeutic relevance. In: Dou QP, editor. Resistance to proteasome inhibitors in cancer. Switzerland Springer International Publishing; 2014. p. 249–74.Google Scholar
  107. 107.
    Grune T, Reinheckel T, Davies KJ. Degradation of oxidized proteins in mammalian cells. FASEB J. 1997;11(7):526–34.PubMedGoogle Scholar
  108. 108.
    Dunlop RA, Brunk UT, Rodgers KJ. Oxidized proteins: mechanisms of removal and consequences of accumulation. IUBMB Life. 2009;61(5):522–7.PubMedCrossRefGoogle Scholar
  109. 109.
    Jung T, Grune T. The proteasome and the degradation of oxidized proteins: part I – structure of proteasomes. Redox Biol. 2013;1(1):178–82.PubMedCentralPubMedCrossRefGoogle Scholar
  110. 110.
    Ott C, Jacobs K, Haucke E, Navarrete Santos A, Grune T, Simm A. Role of advanced glycation end products in cellular signaling. Redox Biol. 2014;2:411–29.PubMedCentralPubMedCrossRefGoogle Scholar
  111. 111.
    Meadows C, Morré DJ, Morré DM, Draelos ZD, Kern D. Age-related NADH oxidase (arNOX)-catalyzed oxidative damage to skin proteins. Arch Dermal Res. 2014;306(7645–852):1–8.Google Scholar
  112. 112.
    Hulbert AJ, Pamplona R, Buffenstein R, Buttemer WA. Life and death: metabolic rate, membrane composition, and life span of animals. Physiol Rev. 2007;87(4):1175–213.PubMedCrossRefGoogle Scholar
  113. 113.
    Thiele JJ, Traber MG, Re R, Espuno N, Yan LJ, Cross CE, et al. Macromolecular carbonyls in human stratum corneum: a biomarker for environmental oxidant exposure? FEBS Lett. 1998;422(3):403–6.PubMedCrossRefGoogle Scholar
  114. 114.
    Sander CS, Chang H, Salzmann S, Muller CSL, Ekanayake-Mudiyanselage S, Elsner P, et al. Photoaging is associated with protein oxidation in human skin in vivo. J Invest Dermatol. 2002;118(4):618–25.PubMedCrossRefGoogle Scholar
  115. 115.
    Hirao T, Takahashi M. Carbonylation of cornified envelopes in the stratum corneum. FEBS Lett. 2005;579(30):6870–4.PubMedCrossRefGoogle Scholar
  116. 116.
    Fisher GJ, Quan T, Purohit T, Shao Y, Cho MK, He T, et al. Collagen fragmentation promotes oxidative stress and elevates matrix metalloproteinase-1 in fibroblasts in aged human skin. Am J Pathol. 2009;174(1):101–14.PubMedCentralPubMedCrossRefGoogle Scholar
  117. 117.
    Larroque-Cardoso P, Camare C, Nadal-Wollbold F, Grazide M-H, Pucelle M, Garoby-Salom S, et al. Elastin modification by 4-hydroxynonenal in hairless mice exposed to UV-A. Role in photoaging and actinic elastosis. J Invest Dermatol. 2015;135:1873–81.PubMedCrossRefGoogle Scholar
  118. 118.
    Thorpe SR, Baynes JW. Maillard reaction products in tissue proteins: new products and new perspectives. Amino Acids. 2003;25(3–4):275–81.PubMedCrossRefGoogle Scholar
  119. 119.
    Gkogkolou P, Böhm M. Advanced glycation end products: key players in skin aging? Derm Endocrinol. 2012;4(3):1–12.Google Scholar
  120. 120.
    Singh R, Barden A, Mori T, Beilin L. Advanced glycation end-products: a review. Diabetologia. 2001;44(2):129–46.PubMedCrossRefGoogle Scholar
  121. 121.
    Jeanmaire C, Danoux L, Pauly G. Glycation during human dermal intrinsic and actinic ageing: an in vivo and in vitro model study. Br J Dermatol. 2001;145(1):10–8.PubMedCrossRefGoogle Scholar
  122. 122.
    Hopps E, Noto D, Caimi G, Averna MR. A novel component of the metabolic syndrome: the oxidative stress. Nutr Metab Cardiovasc Dis. 2010;20(1):72–7.PubMedCrossRefGoogle Scholar
  123. 123.
    Crisan M, Taulescu M, Crisan D, Cosgarea R, Parvu A, Cãtoi C, et al. Expression of advanced glycation end-products on sun-exposed and non-exposed cutaneous sites during the ageing process in humans. PLoS One. 2013;8(10):e75003.PubMedCentralPubMedCrossRefGoogle Scholar
  124. 124.
    Nomoto K, Yagi M, Arita S, Ogura M, Yonei Y. Skin accumulation of advanced glycation end products and lifestyle behaviors in Japanese. J Anti-Aging Med. 2012;9(6):165–73.Google Scholar
  125. 125.
    Ichihashi M, Yagi M, Nomoto K, Yonei Y. Glycation stress and photo-aging in skin. J Anti-aging Med. 2011;8(3):23–9.CrossRefGoogle Scholar
  126. 126.
    Sorci G, Riuzzi F, Giambanco I, Donato R. RAGE in tissue homeostasis, repair and regeneration. Biochim Biophys Acta. 2013;1833(1):101–9.PubMedCrossRefGoogle Scholar
  127. 127.
    Xie J, Méndez JD, Méndez-Valenzuela V, Aguilar-Hernández MM. Cellular signalling of the receptor for advanced glycation end products (RAGE). Cell Signal. 2013;25(11):2185–97.PubMedCrossRefGoogle Scholar
  128. 128.
    Thiele JJ, Schroeter C, Hsieh SN, Podda M, Packer L. The antioxidant network of the stratum corneum. Curr Probl Dermatol. 2001;29:26–42.PubMedCrossRefGoogle Scholar
  129. 129.
    Vermeij WP, Alia A, Backendorf C. ROS quenching potential of the epidermal cornified cell envelope. J Invest Dermatol. 2011;131:1435–41.PubMedCrossRefGoogle Scholar
  130. 130.
    Shindo Y, Witt E, Han D, Epstein W, Packer L. Enzymic and non-enzymic antioxidants in epidermis and dermis of human skin. J Invest Dermatol. 1994;102(1):122–4.PubMedCrossRefGoogle Scholar
  131. 131.
    Vahlquist A, Lee JB, Michaelsson G, Rollman O. Vitamin A in human skin: II concentrations of carotene, retinol and dehydroretinol in various components of normal skin. J Invest Dermatol. 1982;79(2):94–7.PubMedCrossRefGoogle Scholar
  132. 132.
    Leibold JS, Riehl A, Hettinger J, Durben M, Hess J, Angel P. Keratinocyte-specific deletion of the receptor RAGE modulates the kinetics of skin inflammation in vivo. J Invest Dermatol. 2013;133(10):2400–6.PubMedCrossRefGoogle Scholar
  133. 133.
    Kierdorf K, Fritz G. RAGE regulation and signaling in inflammation and beyond. J Leukoc Biol. 2013;94(1):55–68.PubMedCrossRefGoogle Scholar
  134. 134.
    Naylor EC, Watson REB, Sherratt MJ. Molecular aspects of skin ageing. Maturitas. 2011;69(3):249–56.PubMedCrossRefGoogle Scholar
  135. 135.
    Corstjens H, Dicanio D, Muizzuddin N, Neven A, Sparacio R, Declercq L, et al. Glycation associated skin autofluorescence and skin elasticity are related to chronological age and body mass index of healthy subjects. Exp Gerontol. 2008;43(7):663–7.PubMedCrossRefGoogle Scholar
  136. 136.
    Hori M, Yagi M, Nomoto K, Shimode A, Ogura M, Yonei Y. Inhibition of advanced glycation end product formation by herbal teas and its relation to anti-skin aging. Anti-Aging Med. 2012;9:135–48.Google Scholar
  137. 137.
    Antonios V. Drivers of redox status & protein glycation. PhD thesis. Glasgow: University of Glasgow; 2014.
  138. 138.
    Uchida K, Kato Y, Kawakishi S. Metal-catalyzed oxidative degradation of collagen. J Agric Food Chem. 1992;40(1):9–12.CrossRefGoogle Scholar
  139. 139.
    Meinke MC, Müller R, Bechtel A, Haag SF, Darvin ME, Lohan SB, et al. Evaluation of carotenoids and reactive species in human skin after UV irradiation: a critical comparison between in vivo and ex vivo investigations. Exp Dermatol. 2015;24(3):194–7.PubMedCrossRefGoogle Scholar
  140. 140.
    Filomeni G, Rotilio G, Ciriolo MR. Disulfide relays and phosphorylative cascades: partners in redox-mediated signaling pathways. Cell Death Differ. 2005;12(12):1555–63.PubMedCrossRefGoogle Scholar
  141. 141.
    Thiele J, Dreher F, Packer L. Antioxidant defense system in skin. In: Elsner P, Maibach H, editors. Cosmeceuticals-drugs vs cosmetics. New York: Marcel Dekker; 2000. p. 145–88.Google Scholar
  142. 142.
    Pinnell S. Cutaneous photodamage, oxidative stress, and topical antioxidant protection. J Am Acad Dermatol. 2003;48(1):1–19.PubMedCrossRefGoogle Scholar
  143. 143.
    Tiwari A. Imbalance in antioxidant defence and human diseases: multiple approach of natural antioxidants therapy. Curr Sci. 2001;81(9):1179–87.Google Scholar
  144. 144.
    Packer L, Weber SU, Rimbach G. Molecular aspects of alpha-tocotrienol antioxidant action and cell signalling. J Nutr. 2001;131(2):369s–73.PubMedGoogle Scholar
  145. 145.
    Darvin ME, Fluhr JW, Caspers P, van der Pool A, Richter H, Patzelt A, et al. In vivo distribution of carotenoids in different anatomical locations of human skin: comparative assessment with two different Raman spectroscopy methods. Exp Dermatol. 2009;18(12):1060–3.PubMedCrossRefGoogle Scholar
  146. 146.
    Lademann J, Meinke MC, Sterry W, Darvin ME. Carotenoids in human skin. Exp Dermatol. 2011;20(5):377–82.PubMedCrossRefGoogle Scholar
  147. 147.
    Darvin ME, Haag SF, Lademann J, Zastrow L, Sterry W, Meinke MC. Formation of free radicals in human skin during irradiation with infrared light. J Invest Dermatol. 2009;130(2):629–31.PubMedCrossRefGoogle Scholar
  148. 148.
    Darvin M, Haag S, Meinke M, Zastrow L, Sterry W, Lademann J. Radical production by infrared A irradiation in human tissue. Skin Pharmacol Physiol. 2010;23(1):40–6.PubMedCrossRefGoogle Scholar
  149. 149.
    Darvin ME, Fluhr JW, Meinke MC, Zastrow L, Sterry W, Lademann J. Topical beta-carotene protects against infra-red-light–induced free radicals. Exp Dermatol. 2011;20(2):125–9.PubMedCrossRefGoogle Scholar
  150. 150.
    Darvin M, Zastrow L, Sterry W, Lademann J. Effect of supplemented and topically applied antioxidant substances on human tissue. Skin Pharmacol Physiol. 2006;19(5):238–47.PubMedCrossRefGoogle Scholar
  151. 151.
    Meinke MC, Friedrich A, Tscherch K, Haag SF, Darvin ME, Vollert H, et al. Influence of dietary carotenoids on radical scavenging capacity of the skin and skin lipids. Eur J Pharm Biopharm. 2013;84(2):365–73.PubMedCrossRefGoogle Scholar
  152. 152.
    Lademann J, Schanzer S, Meinke M, Sterry W, Darvin ME. Interaction between carotenoids and free radicals in human skin. Skin Pharmacol Physiol. 2011;24(5):238–44.PubMedCrossRefGoogle Scholar
  153. 153.
    Lademann J, Darvin M, Weigmann H-J, Schanzer S, Zastrow L, Douchet O, et al. Sunscreens – UV or light protection. IFSCC Mag. 2014;4:23–8.Google Scholar
  154. 154.
    Svobodova A, Psotova J, Walterova D. Natural phenolics in the prevention of UV-induced skin damage. A review. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2003;147(2):137–45.PubMedCrossRefGoogle Scholar
  155. 155.
    Katiyar SK. Proanthocyanidins from grape seeds inhibit UV radiation-induced immune suppression in mice: detection and analysis of molecular and cellular targets. Photochem Photobiol. 2015;91(1):156–62.PubMedCrossRefPubMedCentralGoogle Scholar
  156. 156.
    Nichols J, Katiyar S. Skin photoprotection by natural polyphenols: anti-inflammatory, antioxidant and DNA repair mechanisms. Arch Dermatol Res. 2010;302(2):71–83.PubMedCentralPubMedCrossRefGoogle Scholar
  157. 157.
    Katiyar S, Elmets C. Green tea and skin cancer: photoimmunology, angiogenesis and DNA repair. J Nutr Biochem. 2007;18(5):287–96.PubMedCrossRefGoogle Scholar
  158. 158.
    Yusuf N, Irby C, Katiyar S, Elmets C. Photoprotective effects of green tea polyphenols. Photodermatol Photoimmunol Photomed. 2007;23:48–56.PubMedCrossRefGoogle Scholar
  159. 159.
    Vermeij WP, Backendorf C, Bridger JM. Skin cornification proteins provide global link between ROS detoxification and cell migration during wound healing. PLoS One. 2010;5(8):996–9.CrossRefGoogle Scholar
  160. 160.
    Schallreuter KU, Wood JM. The role of thioredoxin reductase in the reduction of free radicals at the surface of the epidermis. Biochem Biophys Res Commun. 1986;136(2):630–7.PubMedCrossRefGoogle Scholar
  161. 161.
    Schallreuter KU, Rubsam K, Gibbons NC, Maitland DJ, Chavan B, Zothner C, et al. Methionine sulfoxide reductases A and B are deactivated by hydrogen peroxide (H2O2) in the epidermis of patients with vitiligo. J Invest Dermatol. 2008;128(4):808–15.PubMedCrossRefGoogle Scholar
  162. 162.
    Schallreuter KU. Functioning methionine-S-sulfoxide reductases A and B are present in human skin. J Invest Dermatol. 2006;126(5):947–9.PubMedCrossRefGoogle Scholar
  163. 163.
    Ogawa F, Sander CS, Hansel A, Oehrl W, Kasperczyk H, Elsner P, et al. The repair enzyme peptide methionine-S-sulfoxide reductase is expressed in human epidermis and upregulated by UVA radiation. J Invest Dermatol. 2006;126(5):1128–34.PubMedCrossRefGoogle Scholar
  164. 164.
    Tyrrell RM. Solar ultraviolet A radiation: an oxidizing skin carcinogen that activates heme oxygenase-1. Antioxid Redox Signal. 2004;6(5):835–40.PubMedCrossRefGoogle Scholar
  165. 165.
    Tyrrell RM. Modulation of gene expression by the oxidative stress generated in human skin cells by UVA radiation and the restoration of redox homeostasis. Photochem Photobiol Sci. 2012;11(1):135–47.PubMedCrossRefGoogle Scholar
  166. 166.
    Gozzelino R, Jeney V, Soares MP. Mechanisms of cell protection by heme oxygenase-1. Annu Rev Pharmacol Toxicol. 2010;50:323–54.PubMedCrossRefGoogle Scholar
  167. 167.
    Schallreuter KU, Wood JM. Thioredoxin reductase – its role in epidermal redox status. J Photochem Photobiol B. 2001;64(2–3):179–84.PubMedCrossRefGoogle Scholar
  168. 168.
    Ogawa F, Sander CS, Hansel A, Oehrl W, Kasperczyk H, Elsner P, et al. The repair enzyme peptide methionine-S-sulfoxide reductase is expressed in human epidermis and upregulated by UVA Radiation. J Invest Dermatol. 2006;126(5):1128–34.PubMedCrossRefGoogle Scholar
  169. 169.
    Rhie G, Shin MH, Seo JY, Choi WW, Cho KH, Kim KH, et al. Aging-and photoaging-dependent changes of enzymic and nonenzymic antioxidants in the epidermis and dermis of human skin in vivo. J Invest Dermatol. 2001;117(5):1212–7.PubMedCrossRefGoogle Scholar
  170. 170.
    Lee J, Koo N, Min DB. Reactive oxygen species, aging, and antioxidative nutraceuticals. Compr Rev Food Sci Food Saf. 2004;3(1):21–33.CrossRefGoogle Scholar
  171. 171.
    Constantinescu A, Han D, Packer L. Vitamin E recycling in human erythrocyte membranes. J Biol Chem. 1993;268(15):10906–13.PubMedGoogle Scholar
  172. 172.
    Holmstrom KM, Finkel T. Cellular mechanisms and physiological consequences of redox-dependent signalling. Nat Rev Mol Cell Biol. 2014;15(6):411–21.PubMedCrossRefGoogle Scholar
  173. 173.
    Schieber M, Chandel Navdeep S. ROS function in redox signaling and oxidative stress. Curr Biol. 2014;24(10):R453–62.PubMedCentralPubMedCrossRefGoogle Scholar
  174. 174.
    Yan L-J. Positive oxidative stress in aging and aging-related disease tolerance. Redox Biol. 2014;2:165–9.PubMedCentralCrossRefGoogle Scholar
  175. 175.
    Collins Y, Chouchani ET, James AM, Menger KE, Cochemé HM, Murphy MP. Mitochondrial redox signalling at a glance. J Cell Sci. 2012;125(4):801–6.PubMedCrossRefGoogle Scholar
  176. 176.
    Schulz E, Wenzel P, Munzel T, Daiber A. Mitochondrial redox signaling: interaction of mitochondrial reactive species with other sources of oxidative stress. Antioxid Redox Signal. 2014;20(2):308–24.PubMedCentralPubMedCrossRefGoogle Scholar
  177. 177.
    Wagener FA, Carels CE, Lundvig DM. Targeting the redox balance in inflammatory skin conditions. Int J Mol Sci. 2013;14(5):9126–67.PubMedCentralPubMedCrossRefGoogle Scholar
  178. 178.
    Bito T, Nishigori C. Impact of reactive species on keratinocyte signaling pathways. J Dermatol Sci. 2012;68(1):3–8.PubMedCrossRefGoogle Scholar
  179. 179.
    Trachootham D, Lu W, Ogasawara MA, Nilsa RD, Huang P. Redox regulation of cell survival. Antioxid Redox Signal. 2008;10(8):1343–74.PubMedCentralPubMedCrossRefGoogle Scholar
  180. 180.
    Schafer FQ, Buettner GR. Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radic Biol Med. 2001;30(11):1191–212.PubMedCrossRefGoogle Scholar
  181. 181.
    Sohal RS, Orr WC. The redox stress hypothesis of aging. Free Radic Biol Med. 2012;52(3):539–55.PubMedCentralPubMedCrossRefGoogle Scholar
  182. 182.
    Jones DP. Radical-free biology of oxidative stress. Am J Physiol Cell Physiol. 2008;295(4):C849–68.PubMedCentralPubMedCrossRefGoogle Scholar
  183. 183.
    Beyer TA, auf dem Keller U, Braun S, Schafer M, Werner S. Roles and mechanisms of action of the Nrf2 transcription factor in skin morphogenesis, wound repair and skin cancer. Cell Death Differ. 2007;14(7):1250–4.PubMedCrossRefGoogle Scholar
  184. 184.
    Bhatia M, Karlenius TC, Trapani GD, Tonissen KF. The interaction between redox and hypoxic signalling pathways in the dynamic oxygen environment of cancer cells. In: Tonissen K, editor. Carcinogenesis: Intechopen. 2013. p. 125–52.
  185. 185.
    Osburn WO, Kensler TW. Nrf2 signaling: an adaptive response pathway for protection against environmental toxic insults. Mutat Res. 2008;659(1–2):31–9.PubMedCentralPubMedCrossRefGoogle Scholar
  186. 186.
    Aleksunes LM, Manautou JE. Emerging role of Nrf2 in protecting against hepatic and gastrointestinal disease. Toxicol Pathol. 2007;35(4):459–73.PubMedCrossRefGoogle Scholar
  187. 187.
    Holland R, Fishbein JC. Chemistry of the cysteine sensors in Kelch-like ECH-associated protein 1. Antioxid Redox Signal. 2010;13(11):1749–61.PubMedCentralPubMedCrossRefGoogle Scholar
  188. 188.
    Kaspar JW, Niture SK, Jaiswal AK. Nrf2:INrf2 (Keap1) signaling in oxidative stress. Free Radic Biol Med. 2009;47(9):1304–9.PubMedCentralPubMedCrossRefGoogle Scholar
  189. 189.
    Kansanen E, Kuosmanen SM, Leinonen H, Levonen A-L. The Keap1-Nrf2 pathway: mechanisms of activation and dysregulation in cancer. Redox Biol. 2013;1(1):45–9.PubMedCentralPubMedCrossRefGoogle Scholar
  190. 190.
    Li Y, Paonessa JD, Zhang Y. Mechanism of chemical activation of Nrf2. PLoS One. 2012;7(4):e35122.PubMedCentralPubMedCrossRefGoogle Scholar
  191. 191.
    Hamanaka RB, Chandel NS. Mitochondrial metabolism as a regulator of keratinocyte differentiation. Cell Logist. 2013;3(1):e25456.PubMedCentralPubMedCrossRefGoogle Scholar
  192. 192.
    Hamanaka RB, Glasauer A, Hoover P, Yang S, Blatt H, Mullen AR, et al. Mitochondrial reactive species promote epidermal differentiation and hair follicle development. Sci Signal. 2013;6(261):ra8.PubMedCentralPubMedGoogle Scholar
  193. 193.
    López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013;153(6):1194–217.PubMedCentralPubMedCrossRefGoogle Scholar
  194. 194.
    Medvedev ZA. An attempt at a rational classification of theories of ageing. Biol Rev. 1990;65(3):375–98.PubMedCrossRefGoogle Scholar
  195. 195.
    Harman D. Aging: a theory based on free radical and radiation chemistry. J Gerontol. 1956;11(3):298–300.PubMedCrossRefGoogle Scholar
  196. 196.
    Brieger K, Schiavone S, Miller FJ, Krause K-H. Reactive oxygen species: from health to disease. Swiss Med Wkly. 2012;142:w13659.PubMedGoogle Scholar
  197. 197.
    Harman D. Free radical theory of aging: dietary implications. Am J Clin Nutr. 1972;25(8):839–43.PubMedGoogle Scholar
  198. 198.
    Miquel J, Economos AC, Fleming J, Johnson JE. Mitochondrial role in cell aging. Exp Gerontol. 1980;15(6):575–91.PubMedCrossRefGoogle Scholar
  199. 199.
    Massudi H, Grant R, Braidy N, Guest J, Farnsworth B, Guillemin GJ. Age-associated changes in oxidative stress and NAD+ metabolism in human tissue. PLoS One. 2012;7(7):e42357.PubMedCentralPubMedCrossRefGoogle Scholar
  200. 200.
    Hekimi S, Lapointe J, Wen Y. Taking a “good” look at free radicals in the aging process. Trends Cell Biol. 2011;21(10):569–76.PubMedCentralPubMedCrossRefGoogle Scholar
  201. 201.
    Salmon AB, Richardson A, Pérez VI. Update on the oxidative stress theory of aging: does oxidative stress play a role in aging or healthy aging? Free Radic Biol Med. 2010;48(5):642.PubMedCentralPubMedCrossRefGoogle Scholar
  202. 202.
    Gladyshev VN. The free radical theory of aging is dead. Long live the damage theory! Antioxid Redox Signal. 2013;20(4):727–31.PubMedCrossRefGoogle Scholar
  203. 203.
    Bratic A, Larsson N-G. The role of mitochondria in aging. J Clin Invest. 2013;123(3):951–7.PubMedCentralPubMedCrossRefGoogle Scholar
  204. 204.
    Ristow M, Schmeisser S. Extending life span by increasing oxidative stress. Free Radic Biol Med. 2011;51(2):327–36.PubMedCrossRefGoogle Scholar
  205. 205.
    Newgard CB, Sharpless NE. Coming of age: molecular drivers of aging and therapeutic opportunities. J Clin Invest. 2013;123(3):946–50.PubMedCentralPubMedCrossRefGoogle Scholar
  206. 206.
    Sanz A, Stefanatos RK. The mitochondrial free radical theory of aging: a critical view. Curr Aging Sci. 2008;1(1):10–21.PubMedCrossRefGoogle Scholar
  207. 207.
    Halliwell B. The antioxidant paradox: less paradoxical now? Br J Clin Pharmacol. 2013;75(3):637–44.PubMedCentralPubMedGoogle Scholar
  208. 208.
    Halliwell B. Free radicals and antioxidants: updating a personal view. Nutr Rev. 2012;70(5):257–65.PubMedCrossRefGoogle Scholar
  209. 209.
    Tapia PC. Sublethal mitochondrial stress with an attendant stoichiometric augmentation of reactive species may precipitate many of the beneficial alterations in cellular physiology produced by caloric restriction, intermittent fasting, exercise and dietary phytonutrients: “Mitohormesis” for health and vitality. Med Hypotheses. 2006;66(4):832–43.PubMedCrossRefGoogle Scholar
  210. 210.
    Ristow M, Zarse K. How increased oxidative stress promotes longevity and metabolic health: the concept of mitochondrial hormesis (mitohormesis). Exp Gerontol. 2010;45(6):410–8.PubMedCrossRefGoogle Scholar
  211. 211.
    Liochev SI. Reactive oxygen species and the free radical theory of aging. Free Radic Biol Med. 2013;60:1–4.PubMedCrossRefGoogle Scholar
  212. 212.
    Ristow M. Unraveling the truth about antioxidants: mitohormesis explains ROS-induced health benefits. Nat Med. 2014;20(7):709–11.PubMedCrossRefGoogle Scholar
  213. 213.
    Afanas’ev I. Reactive oxygen species and age-related genes p66shc, sirtuin, FOX03 and klotho in senescence. Oxid Med Cell Longev. 2010;3(2):77–85.PubMedCentralPubMedCrossRefGoogle Scholar
  214. 214.
    Prather AA, Epel ES, Arenander J, Broestl L, Garay BI, Wang D, et al. Longevity factor klotho and chronic psychological stress. Translat Psychiatry. 2015;5:e585.CrossRefGoogle Scholar
  215. 215.
    Rittié L, Fisher GJ. Natural and sun-induced aging of human skin. Cold Spring Harb Perspect Med. 2015;5(1):a015370. doi:10.1101/cshperspect.a015370.Google Scholar
  216. 216.
    Morita A. Tobacco smoke and skin aging. In: Farage M, Miller K, Maibach H, editors. Textbook of aging skin. Berlin/Heidelberg: Springer; 2010. p. 447–50.CrossRefGoogle Scholar
  217. 217.
    Kligman AM. Early destructive effect of sunlight on human skin. JAMA. 1969;210(13):2377–80.PubMedCrossRefGoogle Scholar
  218. 218.
    Kligman L, Kligman A. Photoaging. Manifestations, prevention, and treatment. Dermatol Clin. 1986;4(3):517.PubMedGoogle Scholar
  219. 219.
    Wondrak GT. Let the sun shine in: mechanisms and potential for therapeutics in skin photodamage. Curr Opin Investig Drugs. 2007;8(5):390–400.PubMedGoogle Scholar
  220. 220.
    Mahmoud BH, Hexsel CL, Hamzavi IH, Lim HW. Effects of visible light on the skin. Photochem Photobiol. 2008;84(2):450–62.PubMedCrossRefGoogle Scholar
  221. 221.
    Wolf AM, Nishimaki K, Kamimura N, Ohta S. Real-time monitoring of oxidative stress in live mouse skin. J Invest Dermatol. 2014;134:1701–9.PubMedCrossRefGoogle Scholar
  222. 222.
    Iannacone MR, Hughes MCB, Green AC. Effects of sunscreen on skin cancer and photoaging. Photodermatol Photoimmunol Photomed. 2014;30(2–3):55–61.PubMedCrossRefGoogle Scholar
  223. 223.
    Vierkoetter A, Li M, Ma C, Deng B, Matsui M, Krutmann J, et al. Indoor air pollution from cooking with coal or firewood accelerates skin aging in northern Chinese women. J Invest Dermatol. 2014;132(S51):Abs # 296.Google Scholar
  224. 224.
    Vierkötter A, Krutmann J. Environmental influences on skin aging and ethnic-specific manifestations. Derm Endocrinol. 2012;4(3):227–31.CrossRefGoogle Scholar
  225. 225.
    Vierkötter A, Schikowski T, Ranft U, Sugiri D, Matsui M, Krämer U, et al. Airborne particle exposure and extrinsic skin aging. J Invest Dermatol. 2010;130(12):2719–26.PubMedCrossRefGoogle Scholar
  226. 226.
    He QC, Tavakkol A, Wietecha K, Begum-Gafur R, Ansari SA, Polefka T. Effects of environmentally realistic levels of ozone on stratum corneum function. Int J Cosmet Sci. 2006;28(5):349–57.PubMedCrossRefGoogle Scholar
  227. 227.
    Drakaki E, Dessinioti C, Antoniou CV. Air pollution and the skin. Front Environ Sci. 2014;2:1–6.CrossRefGoogle Scholar
  228. 228.
    Allerhand M, Ting Ooi E, Starr RJ, Alcorn M, Penke L, Drost E, et al. Skin ageing and oxidative stress in a narrow-age cohort of older adults. Eur Geriatr Med. 2011;2(3):140–4.CrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Life Science Solutions, LLCSomersetUSA
  2. 2.Bayer HealthcareMemphisUSA

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