Skip to main content

Hyperpigmentation in Aging Skin

  • Living reference work entry
  • Latest version View entry history
  • First Online:
Textbook of Aging Skin

Abstract

Hyperpigmentation problems, such as postinflammatory hyperpigmentation, solar lentigos, and melasma, can occur across all skin types with aging. Basic understanding of the pigmentation process and of these skin problems has led to their management by attacking proven targets with proven technologies. To name just a few examples, tyrosinase inhibition, blocking melanosome transfer, inhibition of tyrosinase glycosylation, increasing tyrosinase turnover, and blocking inflammation are clinically demonstrated approaches using, respectively, kojic acid, niacinamide, N-acetyl glucosamine, hexyldecanol, and phytosterol. Yet, because of the complexity of the pigmentation process, changes in skin with aging, and the involvement of a variety of cells (melanocytes, keratinocytes, fibroblasts, and inflammatory cells) in initiation, production, and processing of melanin, there are likely many more potential targets still to be characterized and fully exploited.

This review chapter explores these topics. Also, it briefly discusses other important skin chromophores that likely contribute to the color of aging skin, opening further approaches to understand skin color and to develop approaches for treatment of discoloration. Additionally, investigative tools such as laboratory model systems for understanding the pigmentation process and screening for potential active technologies are presented. Furthermore, since evaluating the effectiveness of technology on human subjects is a key step in validating any new approach to treatment, clinical methods are also briefly discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Institutional subscriptions

References

  1. Nordlund JJ, Boissy RE, Hearing VJ, King RA, Ortonne JP. The pigmentary system. New York: Oxford University Press; 1998.

    Google Scholar 

  2. Hearing VJ. Biochemical control of melanogenesis and melanosomal organization. J Investig Dermatol Symp Proc. 1999;4:24–8.

    Article  CAS  PubMed  Google Scholar 

  3. Schallreuter KU. Advances in melanocyte basic science research. Dermatol Clin. 2007;25:283–91.

    Article  CAS  PubMed  Google Scholar 

  4. Cario-Andre M, et al. In vivo and in vitro evidence of dermal fibroblasts influence on human epidermal pigmentation. Pigment Cell Res. 2006;19:434–42.

    Article  PubMed  Google Scholar 

  5. Costin GE, et al. Human skin pigmentation: melanocytes modulate skin color in response to stress. FASEB J. 2007;21:976–94.

    Article  CAS  PubMed  Google Scholar 

  6. Gilchrest BA. Skin and aging processes. Boca Raton: CRC Press; 1984.

    Google Scholar 

  7. Taylor SC. Cosmetic problems in skin of color. Skin Pharmacol Appl Skin Physiol. 1999;12:139–43.

    Article  CAS  PubMed  Google Scholar 

  8. Hachiya A, et al. Biochemical characterization of endothelin-converting enzyme-1 alpha in cultured skin-derived cells and its postulated role in the stimulation of melanogenesis in human epidermis. J Biol Chem. 2002;277:5395–403.

    Article  CAS  PubMed  Google Scholar 

  9. Takiwaki H, et al. The degrees of UVB-induced erythema and pigmentation correlate linearly and are reduced in a parallel manner by topical anti-inflammatory agents. J Invest Dermatol. 1994;103:642–6.

    Article  CAS  PubMed  Google Scholar 

  10. Kadono S, et al. The role of the epidermal endothelin cascade in the hyperpigmentation mechanism of lentigo senilis. J Invest Dermatol. 2001;116:571–7.

    Article  CAS  PubMed  Google Scholar 

  11. Imokawa G. Autocrine and paracrine regulation of melanocytes in human skin and in pigmentary disorders. Pigment Cell Res. 2004;17:96–110.

    Article  CAS  PubMed  Google Scholar 

  12. Cho YH, et al. Changes in skin color after smoking cessation. Korean J Fam Med. 2012;33:105–9.

    Article  PubMed Central  PubMed  Google Scholar 

  13. Noblesse E, et al. Skin ultrastructure in senile lentigo. Skin Pharmacol Physiol. 2006;19:95–100.

    Article  CAS  PubMed  Google Scholar 

  14. Cario-Andre M, et al. Perilesional vs. lesional skin changes in senile lentigo. J Cutan Pathol. 2004;31:441–7.

    Article  PubMed  Google Scholar 

  15. Makrantonaki E, et al. Molecular mechanisms of skin aging: state of the art. Ann N Y Acad Sci. 2007;1119:40–50.

    Article  CAS  PubMed  Google Scholar 

  16. Motokawa T, et al. Messenger RNA levels of melanogenesis-associated genes in lentigo senilis lesions. J Dermatol Sci. 2005;37:120–3.

    Article  CAS  PubMed  Google Scholar 

  17. Unver N, et al. Alterations in the epidermal-dermal melanin axis and factor XIIIa melanophages in senile lentigo and ageing skin. Br J Dermatol. 2006;155:119–28.

    Article  CAS  PubMed  Google Scholar 

  18. Aoki H, et al. Gene expression profiling analysis of solar lentigo in relation to immunohistochemical characteristics. Br J Dermatol. 2007;156:1214–23.

    Article  CAS  PubMed  Google Scholar 

  19. Hakozaki T, et al. The effect of niacinamide on reducing cutaneous pigmentation and suppression of melanosome transfer. Br J Dermatol. 2002;147:20–31.

    Article  CAS  PubMed  Google Scholar 

  20. Bissett DL, et al. Reduction in the appearance of facial hyperpigmentation by topical N-acetyl glucosamine. J Cosmet Dermatol. 2007;6:20–6.

    Article  PubMed  Google Scholar 

  21. Fink B, et al. The effects of skin colour distribution and topography cues on the perception of female facial age and health. J Eur Acad Dermatol Venereol. 2008;22:493–8.

    Article  CAS  PubMed  Google Scholar 

  22. Stephen ID, et al. Facial skin coloration affects perceived health of human faces. Int J Primatol. 2009;30:845–57.

    Article  PubMed Central  PubMed  Google Scholar 

  23. Lieberman R, et al. Estrogen receptor expression in melasma: results from facial skin of affected patients. J Drugs Dermatol. 2008;7:463–5.

    PubMed  Google Scholar 

  24. Kang HY, et al. The dermal stem cell factor and c-kit are overexpressed in melasma. Br J Dermatol. 2006;154:1094–9.

    Article  CAS  PubMed  Google Scholar 

  25. Chi A, et al. Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes. J Proteome Res. 2006;5:3135–44.

    Article  CAS  PubMed  Google Scholar 

  26. Hakozaki T, et al. A regulator of ubiquitin-proteasome activity, 2-hexyldecanol, suppresses melanin synthesis and the appearance of facial hyperpigmented spots. Br J Dermatol. 2013;169S:39–44.

    Article  Google Scholar 

  27. Boissy RE. Melanosome transfer to and translocation in the keratinocyte. Exp Dermatol. 2003;12S2:5–12.

    Article  Google Scholar 

  28. Chen NN, et al. Cathepsin L2 levels inversely correlate with skin color. J Invest Dermatol. 2006;126:2345–7.

    Article  CAS  PubMed  Google Scholar 

  29. Murase D, et al. Autophagy has a significant role in determining skin color by regulating melanosome degradation in keratinocytes. J Invest Dermatol. 2013;133:2416–24.

    Article  CAS  PubMed  Google Scholar 

  30. Ebanks JP, et al. Hydrolytic enzymes of the interfollicular epidermis differ in expression and correlate with the phenotypic difference observed between light and dark skin. J Dermatol. 2012;39:1–7.

    Google Scholar 

  31. Ebanks JP, et al. Epidermal keratinocytes from light vs. dark skin exhibit differential degradation of melanosomes. J Invest Dermatol. 2011; 131:1226–33.

    Article  CAS  PubMed  Google Scholar 

  32. Nakayama H, Ebihara T, Satoh N, Jinnai T. Depigmentation agents. In: Elsner P, Maibach HI, editors. Cosmeceuticals and active cosmetics. Boca Raton: Taylor & Francis; 2005. p. 123–44.

    Google Scholar 

  33. Boissy RE, et al. Deoxyarbutin: a nevel reversible tyrosinase inhibitor with effective in vivo skin lightening potency. Exp Dermatol. 2005;14:601–8.

    Article  CAS  PubMed  Google Scholar 

  34. Chawla S, et al. Mechanism of tyrosinase inhibition by deoxyarbutin and its second-generation derivatives. Br J Dermatol. 2008;159:1267–74.

    Article  CAS  PubMed  Google Scholar 

  35. Bissett DL, et al. Topical niacinamide reduces yellowing, wrinkling, red blotchiness, and hyperpigmented spots in aging facial skin. Int J Cosmet Sci. 2004;26:231–8.

    Article  CAS  PubMed  Google Scholar 

  36. Bissett DL, et al. Reduction in the appearance of facial hyperpigmentation by topical N-undecyl-10-enoyl-L-phenylalanine and its combination with niacinamide. J Cosmet Dermatol. 2009;8:260–6.

    Article  PubMed  Google Scholar 

  37. Navarrete-Solis J, et al. A double-blind, randomized clinical trial of niacinamide 4% versus hydroquinone 4% in the treatment of melasma. Dermatol Res Pract. 2011. doi:10.1155/2011/379173.

    PubMed Central  PubMed  Google Scholar 

  38. Ito S, et al. Tyrosinase-catalyzed oxidation of rhododendrol produces 2-methylchromane-6,7-dione, the putative ultimate toxic metabolite: implications for melanocyte toxicity. Pigment Cell Melanoma Res. 2014. doi:10.1111/pcmr.12275.

    Google Scholar 

  39. Kasamatsu S, et al. Depigmentation caused by application of the active brightening material, rhododendrol, is related to tyrosinase activity at a certain threshold. J Dermatol Sci. 2014;76:16–24.

    Article  CAS  PubMed  Google Scholar 

  40. Kimball AB, et al. Reduction in the appearance of facial hyperpigmentation by a combination of topical niacinamide plus N-acetyl glucosamine: results of a randomized, double-blind, placebo-controlled trial. Br J Dermatol. 2010;162:435–41.

    Article  CAS  PubMed  Google Scholar 

  41. Kim EH, et al. The vascular characteristics of melasma. J Dermatol Sci. 2007;46:111–6.

    Article  CAS  PubMed  Google Scholar 

  42. Dyer DG, et al. Accumulation of maillard reaction products in skin collagen in diabetes and aging. J Clin Invest. 1993;91:2463–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  43. Ohshima H, et al. Melanin and facial skin fluorescence as markers of yellowish discoloration with aging. Skin Res Technol. 2009;15:496–502.

    Article  PubMed  Google Scholar 

  44. Ogura Y, et al. Dermal carbonyl modification is related to the yellowish color change of photo-aged Japanese facial skin. J Dermatol Sci. 2011;64:45–52.

    Article  CAS  PubMed  Google Scholar 

  45. Backvall H, et al. Similar UV responses are seen in a skin organ culture as in human skin in vivo. Exp Dermatol. 2002;11:349–56.

    Article  PubMed  Google Scholar 

  46. Choi T-Y, et al. Zebrafish as a new model for phenotype-based screening of melanogenic regulatory compounds. Pigment Cell Res. 2007;20:120–7.

    Article  CAS  PubMed  Google Scholar 

  47. Furuya R, et al. Changes in the proliferative activity of epidermal melanocytes in serum-free primary culture during the development of ultraviolet radiation B-induced pigmented spots in hairless mice. Pigment Cell Res. 2002;15:348–56.

    Article  PubMed  Google Scholar 

  48. Alaluf S, et al. The impact of epidermal melanin on objective measurements of human skin colour. Pigment Cell Res. 2002;15:119–26.

    Article  CAS  PubMed  Google Scholar 

  49. Matts PJ, et al. The distribution of melanin in skin determined in vivo. Br J Dermatol. 2007;156:620–8.

    Article  CAS  PubMed  Google Scholar 

  50. Nakahima A, et al. Investigation by in vivo reflectance confocal microscopy: melanocytes at the edges of solar lentigenes. Exp Dermatol. 2012;21S1:18–21.

    Article  Google Scholar 

  51. Masuda Y, et al. An innovative method to measure skin pigmentation. Skin Res Technol. 2009;15:224–9.

    Article  PubMed  Google Scholar 

  52. Stamatas GN, et al. In vivo measurement of skin erythema and pigmentation: new means of implementation of diffuse reflectance spectroscopy with a commercial instrument. Br J Dermatol. 2008;159:683–90.

    Article  CAS  PubMed  Google Scholar 

  53. Han X, et al. Near-infrared autofluorescence imaging of cutaneous melanins and human skin in vivo. J Biomed Opt. 2009;14:024017. doi:10.1117/1.3103310.

    Article  PubMed  Google Scholar 

  54. Ravnbak MH, et al. Skin pigmentation kinetics after UVB exposure. Acta Derm Venereol. 2008;88:223–8.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Tomohiro Hakozaki .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer-Verlag Berlin Heidelberg

About this entry

Cite this entry

Hakozaki, T., Swanson, C.L., Bissett, D.L. (2015). Hyperpigmentation in Aging Skin. In: Farage, M., Miller, K., Maibach, H. (eds) Textbook of Aging Skin. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-27814-3_51-3

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-27814-3_51-3

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Online ISBN: 978-3-642-27814-3

  • eBook Packages: Springer Reference MedicineReference Module Medicine

Publish with us

Policies and ethics

Chapter history

  1. Latest

    Hyperpigmentation in Aging Skin
    Published:
    14 November 2015

    DOI: https://doi.org/10.1007/978-3-642-27814-3_51-3

  2. Original

    Hyperpigmentation in Aging Skin
    Published:
    05 August 2015

    DOI: https://doi.org/10.1007/978-3-642-27814-3_51-2