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Aging Skin as a Diagnostic Tool for Internal Diseases: A Chance for Dermatology

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Textbook of Aging Skin

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Abstract

Aged skin is an easily accessible and cost-effective model for the determination of aging of the whole human organism and eventually for the prediction of other age-related comorbidities. Its endogenous variable is called intrinsic aging, while the effect of external factors, such as UV radiation, is termed extrinsic aging. In this overview, key hallmarks, which determine intrinsic aging and extrinsic aging, are mentioned. These include aging of the cellular components of the skin, as well as of the dermal components, i.e., the extracellular matrix. Furthermore, the most common age-related diseases are presented. At last, evidence for the predicting value of aged skin for the development or course of certain pathological conditions is elucidated.

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References

  1. Vina J, et al. Theories of ageing. IUBMB Life. 2007;59:249–54.

    Article  CAS  PubMed  Google Scholar 

  2. Nikolakis G, et al. Skin mirrors human aging. Horm Mol Biol Clin Investig. 2013;16:13–28.

    CAS  PubMed  Google Scholar 

  3. Ganceviciene R, et al. Skin anti-aging strategies. Dermatoendocrinol. 2012;4:308–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Makrantonaki E, et al. Genetics and skin aging. Dermatoendocrinol. 2012;4:280–4.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Kinn PM, et al. Age-dependent variation in cytokines, chemokines, and biologic analytes rinsed from the surface of healthy human skin. Sci Rep. 2015;5:10472.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Zouboulis CC, Makrantonaki E. Clinical aspects and molecular diagnostics of skin aging. Clin Dermatol. 2011;29:3–14.

    Article  PubMed  Google Scholar 

  7. Cevenini E, et al. Human models of aging and longevity. Expert Opin Biol Ther. 2008;8:1393–405.

    Article  CAS  PubMed  Google Scholar 

  8. Callaghan TM, Wilhelm KP. A review of ageing and an examination of clinical methods in the assessment of ageing skin. Part 2: clinical perspectives and clinical methods in the evaluation of ageing skin. Int J Cosmet Sci. 2008;30:323–32.

    Article  CAS  PubMed  Google Scholar 

  9. El-Domyati M, et al. Intrinsic aging vs. photoaging: a comparative histopathological, immunohistochemical, and ultrastructural study of skin. Exp Dermatol. 2002;11:398–405.

    Article  CAS  PubMed  Google Scholar 

  10. Kligman LH. Photoaging. Manifestations, prevention, and treatment. Clin Geriatr Med. 1989;5:235–51.

    CAS  PubMed  Google Scholar 

  11. Lock-Andersen J, et al. Epidermal thickness, skin pigmentation and constitutive photosensitivity. Photodermatol Photoimmunol Photomed. 1997;13:153–8.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  13. Moragas A, et al. Mathematical morphologic analysis of aging-related epidermal changes. Anal Quant Cytol Histol. 1993;15:75–82.

    CAS  PubMed  Google Scholar 

  14. Rawlings AV. Ethnic skin types: are there differences in skin structure and function? Int J Cosmet Sci. 2006;28:79–93.

    Article  CAS  PubMed  Google Scholar 

  15. Chu M, Kollias N. Documentation of normal stratum corneum scaling in an average population: features of differences among age, ethnicity and body site. Br J Dermatol. 2011;164:497–507.

    CAS  PubMed  Google Scholar 

  16. Diridollou S, et al. Comparative study of the hydration of the stratum corneum between four ethnic groups: influence of age. Int J Dermatol. 2007;46 Suppl 1:11–4.

    Article  PubMed  Google Scholar 

  17. Tsukahara K, et al. Comparison of age-related changes in wrinkling and sagging of the skin in Caucasian females and in Japanese females. J Cosmet Sci. 2004;55:351–71.

    PubMed  Google Scholar 

  18. Nouveau-Richard S, et al. Skin ageing: a comparison between Chinese and European populations. A pilot study. J Dermatol Sci. 2005;40:187–93.

    Article  CAS  PubMed  Google Scholar 

  19. Valet F, et al. Assessing the reliability of four severity scales depicting skin ageing features. Br J Dermatol. 2009;161:153–8.

    Article  CAS  PubMed  Google Scholar 

  20. Allsopp RC, et al. Telomere length predicts replicative capacity of human fibroblasts. Proc Natl Acad Sci U S A. 1992;89:10114–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Dimri GP, et al. A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci U S A. 1995;92:9363–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Harman D. The free radical theory of aging. Antioxid Redox Signal. 2003;5:557–61.

    Article  CAS  PubMed  Google Scholar 

  23. Makrantonaki E, et al. Skin and brain age together: the role of hormones in the ageing process. Exp Gerontol. 2010;45:801–13.

    Article  CAS  PubMed  Google Scholar 

  24. Medvedev ZA. An attempt at a rational classification of theories of ageing. Biol Rev Camb Philos Soc. 1990;65:375–98.

    Article  CAS  PubMed  Google Scholar 

  25. Michikawa Y, et al. Aging-dependent large accumulation of point mutations in the human mtDNA control region for replication. Science. 1999;286:774–9.

    Article  CAS  PubMed  Google Scholar 

  26. Mancini M, et al. MicroRNAs in human skin ageing. Ageing Res Rev. 2014;17:9–15.

    Article  CAS  PubMed  Google Scholar 

  27. Janson D, et al. Effects of serially passaged fibroblasts on dermal and epidermal morphogenesis in human skin equivalents. Biogerontology. 2013;14:131–40.

    Article  CAS  PubMed  Google Scholar 

  28. Gilhar A, et al. Ageing of human epidermis: the role of apoptosis, Fas and telomerase. Br J Dermatol. 2004;150:56–63.

    Article  CAS  PubMed  Google Scholar 

  29. Waldera Lupa DM, et al. Characterization of skin aging-associated secreted proteins (SAASP) produced by dermal fibroblasts isolated from intrinsically aged human skin. J Invest Dermatol. 2015;135:1954–68.

    Article  CAS  PubMed  Google Scholar 

  30. Janson D, et al. Papillary fibroblasts differentiate into reticular fibroblasts after prolonged in vitro culture. Exp Dermatol. 2013;22:48–53.

    Article  CAS  PubMed  Google Scholar 

  31. Dos Santos M, et al. In vitro 3-D model based on extending time of culture for studying chronological epidermis aging. Matrix Biol. 2015;47:85–97.

    Article  PubMed  CAS  Google Scholar 

  32. Franceschi C, et al. Human immunosenescence: the prevailing of innate immunity, the failing of clonotypic immunity, and the filling of immunological space. Vaccine. 2000;18:1717–20.

    Article  CAS  PubMed  Google Scholar 

  33. Giacomoni PU, et al. Aging of human skin: review of a mechanistic model and first experimental data. IUBMB Life. 2000;49:259–63.

    Article  CAS  PubMed  Google Scholar 

  34. Linton PJ, Dorshkind K. Age-related changes in lymphocyte development and function. Nat Immunol. 2004;5:133–9.

    Article  CAS  PubMed  Google Scholar 

  35. Plackett TP, et al. Aging and innate immune cells. J Leukoc Biol. 2004;76:291–9.

    Article  CAS  PubMed  Google Scholar 

  36. Plowden J, et al. Innate immunity in aging: impact on macrophage function. Aging Cell. 2004;3:161–7.

    Article  CAS  PubMed  Google Scholar 

  37. Ye J, et al. Alterations in cytokine regulation in aged epidermis: implications for permeability barrier homeostasis and inflammation. I. IL-1 gene family. Exp Dermatol. 2002;11:209–16.

    Article  CAS  PubMed  Google Scholar 

  38. Coppe JP, et al. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol. 2008;6:2853–68.

    Article  CAS  PubMed  Google Scholar 

  39. Freund A, et al. Inflammatory networks during cellular senescence: causes and consequences. Trends Mol Med. 2010;16:238–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Elias PM, Ghadially R. The aged epidermal permeability barrier: basis for functional abnormalities. Clin Geriatr Med. 2002;18:103–20. Vii.

    Article  PubMed  Google Scholar 

  41. Tsutsumi M, Denda M. Paradoxical effects of beta-estradiol on epidermal permeability barrier homeostasis. Br J Dermatol. 2007;157:776–9.

    Article  CAS  PubMed  Google Scholar 

  42. Briganti S, et al. Modulation of PPARgamma provides new insights in a stress induced premature senescence model. PLoS One. 2014;9:e104045.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Robinson MK, et al. Genomic-driven insights into changes in aging skin. J Drugs Dermatol. 2009;8:s8–11.

    PubMed  Google Scholar 

  44. Nikolakis G, et al. Ex vivo human skin and SZ95 sebocytes exhibit a homoeostatic interaction in a novel coculture contact model. Exp Dermatol. 2015;24:497–502.

    Article  CAS  PubMed  Google Scholar 

  45. Engelke M, et al. Effects of xerosis and ageing on epidermal proliferation and differentiation. Br J Dermatol. 1997;137:219–25.

    Article  CAS  PubMed  Google Scholar 

  46. Pochi PE, et al. Age-related changes in sebaceous gland activity. J Invest Dermatol. 1979;73:108–11.

    Article  CAS  PubMed  Google Scholar 

  47. Zouboulis CC, Boschnakow A. Chronological ageing and photoageing of the human sebaceous gland. Clin Exp Dermatol. 2001;26:600–7.

    Article  CAS  PubMed  Google Scholar 

  48. Makrantonaki E, et al. Age-specific hormonal decline is accompanied by transcriptional changes in human sebocytes in vitro. Aging Cell. 2006;5:331–44.

    Article  CAS  PubMed  Google Scholar 

  49. Makrantonaki E, et al. Identification of biomarkers of human skin ageing in both genders. Wnt signalling – a label of skin ageing? PLoS One. 2012;7:e50393.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Chi W, et al. Dermal papilla cell number specifies hair size, shape and cycling and its reduction causes follicular decline. Development. 2013;140:1676–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Yang YC, et al. Androgen receptor accelerates premature senescence of human dermal papilla cells in association with DNA damage. PLoS One. 2013;8:e79434.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Arck PC, et al. Towards a “free radical theory of graying”: melanocyte apoptosis in the aging human hair follicle is an indicator of oxidative stress induced tissue damage. FASEB J. 2006;20:1567–9.

    Article  CAS  PubMed  Google Scholar 

  53. Peters EM, et al. Graying of the human hair follicle. J Cosmet Sci. 2011;62:121–5.

    PubMed  Google Scholar 

  54. Seiberg M. Age-induced hair greying – the multiple effects of oxidative stress. Int J Cosmet Sci. 2013;35:532–8.

    Article  CAS  PubMed  Google Scholar 

  55. Schuler N, Rube CE. Accumulation of DNA damage-induced chromatin alterations in tissue-specific stem cells: the driving force of aging? PLoS One. 2013;8:e63932.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Inoue M, Katakami C. The effect of hyaluronic acid on corneal epithelial cell proliferation. Invest Ophthalmol Vis Sci. 1993;34:2313–5.

    CAS  PubMed  Google Scholar 

  57. Toole BP. Hyaluronan in morphogenesis. J Intern Med. 1997;242:35–40.

    Article  CAS  PubMed  Google Scholar 

  58. Baumann L. Skin ageing and its treatment. J Pathol. 2007;211:241–51.

    Article  CAS  PubMed  Google Scholar 

  59. Papakonstantinou E, et al. Hyaluronic acid: a key molecule in skin aging. Dermatoendocrinol. 2012;4:253–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Shapiro SD. Matrix metalloproteinase degradation of extracellular matrix: biological consequences. Curr Opin Cell Biol. 1998;10:602–8.

    Article  CAS  PubMed  Google Scholar 

  61. Isnard N, et al. Regulation of elastase-type endopeptidase activity, MMP-2 and MMP-9 expression and activation in human dermal fibroblasts by fucose and a fucose-rich polysaccharide. Biomed Pharmacother. 2002;56:258–64.

    Article  CAS  PubMed  Google Scholar 

  62. Longas MO, et al. Evidence for structural changes in dermatan sulfate and hyaluronic acid with aging. Carbohydr Res. 1987;159:127–36.

    Article  CAS  PubMed  Google Scholar 

  63. Meyer LJ, Stern R. Age-dependent changes of hyaluronan in human skin. J Invest Dermatol. 1994;102:385–9.

    Article  CAS  PubMed  Google Scholar 

  64. Rock K, et al. miR-23a-3p causes cellular senescence by targeting hyaluronan synthase 2: possible implication for skin aging. J Invest Dermatol. 2015;135:369–77.

    Article  PubMed  CAS  Google Scholar 

  65. Isnard N, et al. Effect of sulfated GAGs on the expression and activation of MMP-2 and MMP-9 in corneal and dermal explant cultures. Cell Biol Int. 2003;27:779–84.

    Article  CAS  PubMed  Google Scholar 

  66. Langton AK, et al. A new wrinkle on old skin: the role of elastic fibres in skin ageing. Int J Cosmet Sci. 2010;32:330–9.

    Article  CAS  PubMed  Google Scholar 

  67. Naylor EC, et al. Molecular aspects of skin ageing. Maturitas. 2011;69:249–56.

    Article  CAS  PubMed  Google Scholar 

  68. Park HY, et al. A long-standing hyperglycaemic condition impairs skin barrier by accelerating skin ageing process. Exp Dermatol. 2011;20:969–74.

    Article  CAS  PubMed  Google Scholar 

  69. Paul RG, Bailey AJ. Glycation of collagen: the basis of its central role in the late complications of ageing and diabetes. Int J Biochem Cell Biol. 1996;28:1297–310.

    Article  CAS  PubMed  Google Scholar 

  70. Bierhaus A, et al. Understanding RAGE, the receptor for advanced glycation end products. J Mol Med (Berl). 2005;83:876–86.

    Article  CAS  Google Scholar 

  71. Fleming TH, et al. Reactive metabolites and AGE/RAGE-mediated cellular dysfunction affect the aging process: a mini-review. Gerontology. 2011;57:435–43.

    CAS  PubMed  Google Scholar 

  72. Gkogkolou P, Bohm M. Advanced glycation end products: key players in skin aging? Dermatoendocrinol. 2012;4:259–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Cerami C, et al. Tobacco smoke is a source of toxic reactive glycation products. Proc Natl Acad Sci U S A. 1997;94:13915–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Glenn JV, et al. Confocal Raman microscopy can quantify advanced glycation end product (AGE) modifications in Bruch’s membrane leading to accurate, nondestructive prediction of ocular aging. FASEB J. 2007;21:3542–52.

    Article  CAS  PubMed  Google Scholar 

  75. Sell DR, et al. Differential effects of type 2 (non-insulin-dependent) diabetes mellitus on pentosidine formation in skin and glomerular basement membrane. Diabetologia. 1993;36:936–41.

    Article  CAS  PubMed  Google Scholar 

  76. Stitt AW. Advanced glycation: an important pathological event in diabetic and age related ocular disease. Br J Ophthalmol. 2001;85:746–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Vlassara H, et al. Inflammatory mediators are induced by dietary glycotoxins, a major risk factor for diabetic angiopathy. Proc Natl Acad Sci U S A. 2002;99:15596–601.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Thijssen DH et al. Arterial structure and function in vascular ageing: “Are you as old as your arteries?”. J Physiol. 2015.

    Google Scholar 

  79. Wang Y, et al. Effect of glucose on the biomechanical function of arterial elastin. J Mech Behav Biomed Mater. 2015;49:244–54.

    Article  PubMed  CAS  Google Scholar 

  80. Fang M, et al. Advanced glycation end-products accelerate the cardiac aging process through the receptor for advanced glycation end-products/transforming growth factor-beta-Smad signaling pathway in cardiac fibroblasts. Geriatr Gerontol Int. 2015;28:12499.

    Google Scholar 

  81. Wu X, Monnier VM. Enzymatic deglycation of proteins. Arch Biochem Biophys. 2003;419:16–24.

    Article  CAS  PubMed  Google Scholar 

  82. Xue M, et al. Glyoxalase in ageing. Semin Cell Dev Biol. 2011;22:293–301.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Jeanmaire C, et al. Glycation during human dermal intrinsic and actinic ageing: an in vivo and in vitro model study. Br J Dermatol. 2001;145:10–8.

    Article  CAS  PubMed  Google Scholar 

  85. Avery NC, Bailey AJ. The effects of the Maillard reaction on the physical properties and cell interactions of collagen. Pathol Biol (Paris). 2006;54:387–95.

    Article  CAS  Google Scholar 

  86. Degroot J, et al. Age-related decrease in susceptibility of human articular cartilage to matrix metalloproteinase-mediated degradation: the role of advanced glycation end products. Arthritis Rheum. 2001;44:2562–71.

    Article  CAS  PubMed  Google Scholar 

  87. Mizutari K, et al. Photo-enhanced modification of human skin elastin in actinic elastosis by N(epsilon)-(carboxymethyl)lysine, one of the glycoxidation products of the Maillard reaction. J Invest Dermatol. 1997;108:797–802.

    Article  CAS  PubMed  Google Scholar 

  88. Alikhani Z, et al. Advanced glycation end products enhance expression of pro-apoptotic genes and stimulate fibroblast apoptosis through cytoplasmic and mitochondrial pathways. J Biol Chem. 2005;280:12087–95.

    Article  CAS  PubMed  Google Scholar 

  89. Zhu P, et al. Impairment of human keratinocyte mobility and proliferation by advanced glycation end products-modified BSA. Arch Dermatol Res. 2011;303:339–50.

    Article  CAS  PubMed  Google Scholar 

  90. Berge U, et al. Sugar-induced premature aging and altered differentiation in human epidermal keratinocytes. Ann N Y Acad Sci. 2007;1100:524–9.

    Article  CAS  PubMed  Google Scholar 

  91. Ravelojaona V, et al. Expression of senescence-associated beta-galactosidase (SA-beta-Gal) by human skin fibroblasts, effect of advanced glycation end-products and fucose or rhamnose-rich polysaccharides. Arch Gerontol Geriatr. 2009;48:151–4.

    Article  CAS  PubMed  Google Scholar 

  92. Sejersen H, Rattan SI. Dicarbonyl-induced accelerated aging in vitro in human skin fibroblasts. Biogerontology. 2009;10:203–11.

    Article  CAS  PubMed  Google Scholar 

  93. Hofmann B, et al. Advanced glycation end product associated skin autofluorescence: a mirror of vascular function? Exp Gerontol. 2013;48:38–44.

    Article  CAS  PubMed  Google Scholar 

  94. Yamagishi S, et al. Evaluation of tissue accumulation levels of advanced glycation end products by skin autofluorescence: a novel marker of vascular complications in high-risk patients for cardiovascular disease. Int J Cardiol. 2015;185:263–8.

    Article  PubMed  Google Scholar 

  95. Pennacchi PC, et al. Glycated reconstructed human skin as a platform to study pathogenesis of skin aging. Tissue Eng Part A. 2015;1:1.

    Google Scholar 

  96. Poundarik AA, et al. A direct role of collagen glycation in bone fracture. J Mech Behav Biomed Mater. 2015;50:82–92.

    Article  Google Scholar 

  97. Sestier B. [Hematopoietic stem cell exhaustion and advanced glycation end-products in the unexplained anemia of the elderly]. Rev Esp Geriatr Gerontol. 2015;50:223–31.

    Article  PubMed  Google Scholar 

  98. Kandarakis SA, et al. Dietary glycotoxins induce RAGE and VEGF up-regulation in the retina of normal rats. Exp Eye Res. 2015;137:1–10.

    Article  CAS  PubMed  Google Scholar 

  99. Zolla V, et al. Aging-related anatomical and biochemical changes in lymphatic collectors impair lymph transport, fluid homeostasis, and pathogen clearance. Aging Cell. 2015;14:582–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Fuchs E, Chen T. A matter of life and death: self-renewal in stem cells. EMBO Rep. 2013;14:39–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Thomson JA, et al. Embryonic stem cell lines derived from human blastocysts. Science. 1998;282:1145–7.

    Article  CAS  PubMed  Google Scholar 

  102. Zouboulis CC, et al. Human skin stem cells and the ageing process. Exp Gerontol. 2008;43:986–97.

    Article  CAS  PubMed  Google Scholar 

  103. Potten CS. The epidermal proliferative unit: the possible role of the central basal cell. Cell Tissue Kinet. 1974;7:77–88.

    CAS  PubMed  Google Scholar 

  104. Biernaskie JA, et al. Isolation of skin-derived precursors (SKPs) and differentiation and enrichment of their Schwann cell progeny. Nat Protoc. 2006;1:2803–12.

    Article  CAS  PubMed  Google Scholar 

  105. Chen FG, et al. Clonal analysis of nestin(−) vimentin(+) multipotent fibroblasts isolated from human dermis. J Cell Sci. 2007;120:2875–83.

    Article  CAS  PubMed  Google Scholar 

  106. Kim J-H, et al. Adipose-derived stem cells as a new therapeutic modality for ageing skin. Exp Dermatol. 2011;20:383–7.

    Article  CAS  PubMed  Google Scholar 

  107. Yang YI, et al. Ex vivo organ culture of adipose tissue for in situ mobilization of adipose-derived stem cells and defining the stem cell niche. J Cell Physiol. 2010;224:807–16.

    Article  CAS  PubMed  Google Scholar 

  108. Grove GL, Kligman AM. Age-associated changes in human epidermal cell renewal. J Gerontol. 1983;38:137–42.

    Article  CAS  PubMed  Google Scholar 

  109. Racila D, Bickenbach JR. Are epidermal stem cells unique with respect to aging? Aging (Albany NY). 2009;1:746–50.

    Article  Google Scholar 

  110. Conboy IM, et al. Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature. 2005;433:760–4.

    Article  CAS  PubMed  Google Scholar 

  111. Sharpless NE, Depinho RA. How stem cells age and why this makes us grow old. Nat Rev Mol Cell Biol. 2007;8:703–13.

    Article  CAS  PubMed  Google Scholar 

  112. Barrandon Y, Green H. Three clonal types of keratinocyte with different capacities for multiplication. Proc Natl Acad Sci U S A. 1987;84:2302–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Ressler S, et al. p16INK4A is a robust in vivo biomarker of cellular aging in human skin. Aging Cell. 2006;5:379–89.

    Article  CAS  PubMed  Google Scholar 

  114. Giangreco A, et al. Human skin aging is associated with reduced expression of the stem cell markers beta1 integrin and MCSP. J Invest Dermatol. 2010;130:604–8.

    Article  CAS  PubMed  Google Scholar 

  115. Ruzankina Y, et al. Deletion of the developmentally essential gene ATR in adult mice leads to age-related phenotypes and stem cell loss. Cell Stem Cell. 2007;1:113–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Giangreco A, et al. Epidermal stem cells are retained in vivo throughout skin aging. Aging Cell. 2008;7:250–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Stern MM, Bickenbach JR. Epidermal stem cells are resistant to cellular aging. Aging Cell. 2007;6:439–52.

    Article  CAS  PubMed  Google Scholar 

  118. Asumda FZ. Age-associated changes in the ecological niche: implications for mesenchymal stem cell aging. Stem Cell Res Ther. 2013;4:47.

    Article  PubMed  PubMed Central  Google Scholar 

  119. Doles J, et al. Age-associated inflammation inhibits epidermal stem cell function. Genes Dev. 2012;26:2144–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Bromberg JF, et al. Stat3 as an oncogene. Cell. 1999;98:295–303.

    Article  CAS  PubMed  Google Scholar 

  121. Demaria M, et al. STAT3 can serve as a hit in the process of malignant transformation of primary cells. Cell Death Differ. 2012;19:1390–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Demaria M, Poli V. Pro-malignant properties of STAT3 during chronic inflammation. Oncotarget. 2012;3:359–60.

    Article  PubMed  PubMed Central  Google Scholar 

  123. Castilho RM, et al. mTOR mediates Wnt-induced epidermal stem cell exhaustion and aging. Cell Stem Cell. 2009;5:279–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Biernaskie J, et al. SKPs derive from hair follicle precursors and exhibit properties of adult dermal stem cells. Cell Stem Cell. 2009;5:610–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Liu S, et al. The PI3K-Akt pathway inhibits senescence and promotes self-renewal of human skin-derived precursors in vitro. Aging Cell. 2011;10:661–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Beaudry VG, Attardi LD. SKP-ing TAp63: stem cell depletion, senescence, and premature aging. Cell Stem Cell. 2009;5:1–2.

    Article  CAS  PubMed  Google Scholar 

  127. Paris M, et al. Regulation of skin aging and heart development by TAp63. Cell Death Differ. 2012;19:186–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Su X, Flores ER. TAp63: the fountain of youth. Aging (Albany NY). 2009;1:866–9.

    Article  CAS  PubMed Central  Google Scholar 

  129. Bufalino MR, et al. The asymmetric segregation of damaged proteins is stem cell-type dependent. J Cell Biol. 2013;201:523–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Florian MC, Geiger H. Concise review: polarity in stem cells, disease, and aging. Stem Cells. 2010;28:1623–9.

    Article  PubMed  PubMed Central  Google Scholar 

  131. Chung JH, et al. Decreased extracellular-signal-regulated kinase and increased stress-activated MAP kinase activities in aged human skin in vivo. J Invest Dermatol. 2000;115:177–82.

    Article  CAS  PubMed  Google Scholar 

  132. Bernstein EF, et al. Enhanced elastin and fibrillin gene expression in chronically photodamaged skin. J Invest Dermatol. 1994;103:182–6.

    Article  CAS  PubMed  Google Scholar 

  133. Mitchell RE. Chronic solar dermatosis: a light and electron microscopic study of the dermis. J Invest Dermatol. 1967;48:203–20.

    Article  CAS  PubMed  Google Scholar 

  134. Berneburg M, et al. Chronically ultraviolet-exposed human skin shows a higher mutation frequency of mitochondrial DNA as compared to unexposed skin and the hematopoietic system. Photochem Photobiol. 1997;66:271–5.

    Article  CAS  PubMed  Google Scholar 

  135. Sugimoto M, et al. Telomere length of the skin in association with chronological aging and photoaging. J Dermatol Sci. 2006;43:43–7.

    Article  CAS  PubMed  Google Scholar 

  136. Gilchrest BA. A review of skin ageing and its medical therapy. Br J Dermatol. 1996;135:867–75.

    Article  CAS  PubMed  Google Scholar 

  137. Ernster VL, et al. Facial wrinkling in men and women, by smoking status. Am J Public Health. 1995;85:78–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Kadunce DP, et al. Cigarette smoking: risk factor for premature facial wrinkling. Ann Intern Med. 1991;114:840–4.

    Article  CAS  PubMed  Google Scholar 

  139. Yin L, et al. Skin aging induced by ultraviolet exposure and tobacco smoking: evidence from epidemiological and molecular studies. Photodermatol Photoimmunol Photomed. 2001;17:178–83.

    Article  CAS  PubMed  Google Scholar 

  140. Just M, et al. Effect of smoking on skin elastic fibres: morphometric and immunohistochemical analysis. Br J Dermatol. 2007;156:85–91.

    Article  CAS  PubMed  Google Scholar 

  141. Model D. Smoker’s face: an underrated clinical sign? Br Med J (Clin Res Ed). 1985;291:1760–2.

    Article  CAS  Google Scholar 

  142. Tzellos TG, et al. Differential hyaluronan homeostasis and expression of proteoglycans in juvenile and adult human skin. J Dermatol Sci. 2011;61:69–72.

    Article  CAS  PubMed  Google Scholar 

  143. Makrantonaki E, et al. Skin diseases in geriatric patients. Epidemiologic data. Hautarzt. 2012;63:938–46.

    Article  CAS  PubMed  Google Scholar 

  144. Eklof B, et al. Updated terminology of chronic venous disorders: the VEIN-TERM transatlantic interdisciplinary consensus document. J Vasc Surg. 2009;49:498–501.

    Article  PubMed  Google Scholar 

  145. Nicolaides AN, et al. Management of chronic venous disorders of the lower limbs: guidelines according to scientific evidence. Int Angiol. 2008;27:1–59.

    CAS  PubMed  Google Scholar 

  146. Rabe E, et al. Epidemiology of chronic venous disorders in geographically diverse populations: results from the Vein Consult Program. Int Angiol. 2012;31:105–15.

    CAS  PubMed  Google Scholar 

  147. Dissemond J. Medications. A rare cause for leg ulcers. Hautarzt. 2011;62:516–23.

    Article  CAS  PubMed  Google Scholar 

  148. Theisen S, et al. Pressure ulcers in older hospitalised patients and its impact on length of stay: a retrospective observational study. J Clin Nurs. 2012;21:380–7.

    Article  PubMed  Google Scholar 

  149. Laube S, Farrell AM. Bacterial skin infections in the elderly: diagnosis and treatment. Drugs Aging. 2002;19:331–42.

    Article  PubMed  Google Scholar 

  150. Na CR, et al. Elderly adults and skin disorders: common problems for nondermatologists. South Med J. 2012;105:600–6.

    Article  PubMed  Google Scholar 

  151. Gilchrest BA, et al. Effect of chronologic aging and ultraviolet irradiation on Langerhans cells in human epidermis. J Invest Dermatol. 1982;79:85–8.

    Article  CAS  PubMed  Google Scholar 

  152. Sunderkotter C, et al. Aging and the skin immune system. Arch Dermatol. 1997;133:1256–62.

    Article  CAS  PubMed  Google Scholar 

  153. Schmidt E, Zillikens D. Diagnosis and clinical severity markers of bullous pemphigoid. F1000 Med Rep 1. 2009.

    Google Scholar 

  154. Ingen-Housz-Oro S, et al. Pemphigus in elderly adults: clinical presentation, treatment, and prognosis. J Am Geriatr Soc. 2012;60:1185–7.

    Article  PubMed  Google Scholar 

  155. Langan SM, et al. Bullous pemphigoid and pemphigus vulgaris–incidence and mortality in the UK: population based cohort study. BMJ. 2008;337:a180.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Ejaz A, et al. Presentation of early onset psoriasis in comparison with late onset psoriasis: a clinical study from Pakistan. Indian J Dermatol Venereol Leprol. 2009;75:36–40.

    Article  PubMed  Google Scholar 

  157. Ferrandiz C, et al. Psoriasis of early and late onset: a clinical and epidemiologic study from Spain. J Am Acad Dermatol. 2002;46:867–73.

    Article  PubMed  Google Scholar 

  158. Kwon HH, et al. Clinical study of psoriasis occurring over the age of 60 years: is elderly-onset psoriasis a distinct subtype? Int J Dermatol. 2012;51:53–8.

    Article  PubMed  Google Scholar 

  159. Bellei B, et al. Vitiligo: a possible model of degenerative diseases. PLoS One. 2013;8:e59782.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Gallagher RP. Sunscreens in melanoma and skin cancer prevention. CMAJ. 2005;173:244–5.

    Article  PubMed  PubMed Central  Google Scholar 

  161. Goldberg LH, Mamelak AJ. Review of actinic keratosis. Part I: etiology, epidemiology and clinical presentation. J Drugs Dermatol. 2010;9:1125–32.

    PubMed  Google Scholar 

  162. Schmitt JV, Miot HA. Actinic keratosis: a clinical and epidemiological revision. An Bras Dermatol. 2012;87:425–34.

    Article  PubMed  Google Scholar 

  163. Traianou A, et al. Risk factors for actinic keratosis in eight European centres: a case–control study. Br J Dermatol. 2012;167 Suppl 2:36–42.

    Article  PubMed  Google Scholar 

  164. Baxter JM, et al. Facial basal cell carcinoma. BMJ. 2012;345:e5342.

    Article  PubMed  CAS  Google Scholar 

  165. Bath-Hextall F, et al. Trends in incidence of skin basal cell carcinoma. Additional evidence from a UK primary care database study. Int J Cancer. 2007;121:2105–8.

    Article  CAS  PubMed  Google Scholar 

  166. Perrotta RE, et al. Non-melanoma skin cancers in elderly patients. Crit Rev Oncol Hematol. 2011;80:474–80.

    Article  PubMed  Google Scholar 

  167. Samarasinghe V, Madan V. Nonmelanoma skin cancer. J Cutan Aesthet Surg. 2012;5:3–10.

    Article  PubMed  PubMed Central  Google Scholar 

  168. Chamberlain AJ, et al. Nodular type and older age as the most significant associations of thick melanoma in Victoria, Australia. Arch Dermatol. 2002;138:609–14.

    Article  PubMed  Google Scholar 

  169. Chang AE, et al. The National Cancer Data Base report on cutaneous and noncutaneous melanoma: a summary of 84,836 cases from the past decade. The American College of Surgeons Commission on Cancer and the American Cancer Society. Cancer. 1998;83:1664–78.

    Article  CAS  PubMed  Google Scholar 

  170. Lasithiotakis KG, et al. The incidence and mortality of cutaneous melanoma in Southern Germany: trends by anatomic site and pathologic characteristics, 1976 to 2003. Cancer. 2006;107:1331–9.

    Article  PubMed  Google Scholar 

  171. Macdonald JB, et al. Malignant melanoma in the elderly: different regional disease and poorer prognosis. J Cancer. 2011;2:538–43.

    Article  PubMed  PubMed Central  Google Scholar 

  172. Swetter SM, et al. Melanoma in the older person. Oncology (Williston Park). 2004;18:1187–96; discussion 1196–1187.

    Google Scholar 

  173. Tsai S, et al. Epidemiology and treatment of melanoma in elderly patients. Nat Rev Clin Oncol. 2010;7:148–52.

    Article  PubMed  Google Scholar 

  174. Makrantonaki E, et al. Interplay of IGF-I and 17beta-estradiol at age-specific levels in human sebocytes and fibroblasts in vitro. Exp Gerontol. 2008;43:939–46.

    Article  CAS  PubMed  Google Scholar 

  175. Laron Z. Do deficiencies in growth hormone and insulin-like growth factor-1 (IGF-1) shorten or prolong longevity? Mech Ageing Dev. 2005;126:305–7.

    Article  CAS  PubMed  Google Scholar 

  176. Tomlinson JW, et al. Association between premature mortality and hypopituitarism. The Lancet. 2001;357:425–31.

    Article  CAS  Google Scholar 

  177. Zouboulis CC, et al. Sexual hormones in human skin. Horm Metab Res. 2007;39:85–95.

    Article  CAS  PubMed  Google Scholar 

  178. Herzog V, et al. Biological roles of APP in the epidermis. Eur J Cell Biol. 2004;83:613–24.

    Article  CAS  PubMed  Google Scholar 

  179. Kvetnoi IM, et al. Expression of beta-amyloid and tau-protein in mastocytes in Alzheimer disease. Arkh Patol. 2003;65:36–9.

    CAS  PubMed  Google Scholar 

  180. Yaar M, Gilchrest BA. Human melanocytes as a model system for studies of Alzheimer disease. Arch Dermatol. 1997;133:1287–91.

    Article  CAS  PubMed  Google Scholar 

  181. Hossini AM, et al. Induced pluripotent stem cell-derived neuronal cells from a sporadic Alzheimer’s disease donor as a model for investigating AD-associated gene regulatory networks. BMC Genomics. 2015;16:015–1262.

    Article  CAS  Google Scholar 

  182. Mukherjee A, Swarnakar S. Implication of matrix metalloproteinases in regulating neuronal disorder. Mol Biol Rep. 2015;42:1–11.

    Article  CAS  PubMed  Google Scholar 

  183. Debusk FL. The Hutchinson-Gilford progeria syndrome. Report of 4 cases and review of the literature. J Pediatr. 1972;80:697–724.

    Article  CAS  PubMed  Google Scholar 

  184. Merideth MA, et al. Phenotype and course of Hutchinson-Gilford progeria syndrome. N Engl J Med. 2008;358:592–604.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  185. Scaffidi P, Misteli T. Lamin A-dependent misregulation of adult stem cells associated with accelerated ageing. Nat Cell Biol. 2008;10:452–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  186. Wenzel V, et al. Naive adult stem cells from patients with Hutchinson-Gilford progeria syndrome express low levels of progerin in vivo. Biol Open. 2012;1:516–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Mcclintock D, et al. The mutant form of lamin A that causes Hutchinson-Gilford progeria is a biomarker of cellular aging in human skin. PLoS One. 2007;2:e1269.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  188. Rosengardten Y, et al. Stem cell depletion in Hutchinson-Gilford progeria syndrome. Aging Cell. 2011;10:1011–20.

    Article  CAS  PubMed  Google Scholar 

  189. Capell BC, et al. From the rarest to the most common: insights from progeroid syndromes into skin cancer and aging. J Invest Dermatol. 2009;129:2340–50.

    Article  CAS  PubMed  Google Scholar 

  190. Davis T, et al. The role of cellular senescence in Werner syndrome: toward therapeutic intervention in human premature aging. Ann N Y Acad Sci. 2007;1100:455–69.

    Article  CAS  PubMed  Google Scholar 

  191. Winkelspecht K, et al. Metageria–clinical manifestations of a premature aging syndrome. Hautarzt. 1997;48:657–61.

    Article  CAS  PubMed  Google Scholar 

  192. Sakai S, et al. Functional properties of the stratum corneum in patients with diabetes mellitus: similarities to senile xerosis. Br J Dermatol. 2005;153:319–23.

    Article  CAS  PubMed  Google Scholar 

  193. Braverman IM. Elastic fiber and microvascular abnormalities in aging skin. Clin Geriatr Med. 1989;5:69–90.

    CAS  PubMed  Google Scholar 

  194. Petrofsky J, et al. The influence of aging and diabetes on heat transfer characteristics of the skin to a rapidly applied heat source. Diabetes Technol Ther. 2010;12:1003–10.

    Article  PubMed  Google Scholar 

  195. Petrofsky JS, et al. Skin heat dissipation: the influence of diabetes, skin thickness, and subcutaneous fat thickness. Diabetes Technol Ther. 2008;10:487–93.

    Article  PubMed  Google Scholar 

  196. Monami M, et al. Skin autofluorescence in type 2 diabetes: beyond blood glucose. Diabetes Res Clin Pract. 2008;79:56–60.

    Article  CAS  PubMed  Google Scholar 

  197. Lutgers HL, et al. Skin autofluorescence as a noninvasive marker of vascular damage in patients with type 2 diabetes. Diabetes Care. 2006;29:2654–9.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Auenweg 38, 06847, Dessau, Germany

    Georgios Nikolakis, Evgenia Makrantonaki & Christos C. Zouboulis

  2. Geriatry Research Group, Charité Universitaetsmedizin Berlin, Berlin, Germany

    Evgenia Makrantonaki

  3. Department of Dermatology and Allergology, University Medical Center Ulm, Ulm, Germany

    Evgenia Makrantonaki

Authors
  1. Georgios Nikolakis
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  2. Evgenia Makrantonaki
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  3. Christos C. Zouboulis
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Correspondence to Christos C. Zouboulis .

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Editors and Affiliations

  1. Procter & Gamble Co., Cincinnati, Ohio, USA

    Miranda A. Farage

  2. Procter & Gamble Co., Cincinnati, Ohio, USA

    Kenneth W. Miller

  3. Department Dermatology, University of California, San Francisco School of Medicine, San Francisco, California, USA

    Howard I. Maibach

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Nikolakis, G., Makrantonaki, E., Zouboulis, C. (2015). Aging Skin as a Diagnostic Tool for Internal Diseases: A Chance for Dermatology. 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_125-1

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  • Online ISBN: 978-3-642-27814-3

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