Skip to main content
Erschienen in: Der Hautarzt 2/2016

01.02.2016 | Hautalterung | Leitthema

Experimentelle Modelle humaner Hautalterung

verfasst von: G. Nikolakis, C. Zoschke, E. Makrantonaki, C. Hausmann, M. Schäfer-Korting, Prof. Dr. med. Prof. h.c. Dr. h.c. C. C. Zouboulis

Erschienen in: Die Dermatologie | Ausgabe 2/2016

Einloggen, um Zugang zu erhalten

Zusammenfassung

Die Haut stellt ein repräsentatives Model für die Erforschung der humanen Alterung dar. Trotz hoher regenerativer Kapazität der Haut verändert sich die Hautphysiologie im Laufe des Lebens. Die medizinische als auch die kosmetische Forschung versuchen Alterungsprozessen vorzubeugen, diese zu verlangsamen, anzuhalten oder umzukehren. Auswirkungen der alternsassoziierten DNA-Schäden und strukturellen Hautveränderungen auf pharmakologische Parameter sind größtenteils unbekannt. Dieser Übersichtsartikel fasst den Stand der Wissenschaft im Bereich experimenteller Modelle humaner Hautalterung zusammen und zeigt Ansätze zur Verbesserung organotypischer Hautmodelle auf, um prädiktive Modelle der Hautalterung zu entwickeln und die Alterungsforschung zu verbessern.
Literatur
1.
Zurück zum Zitat Akase T, Nagase T, Huang L et al (2012) Aging-like skin changes induced by ultraviolet irradiation in an animal model of metabolic syndrome. Biol Res Nurs 14:180–187CrossRefPubMed Akase T, Nagase T, Huang L et al (2012) Aging-like skin changes induced by ultraviolet irradiation in an animal model of metabolic syndrome. Biol Res Nurs 14:180–187CrossRefPubMed
2.
Zurück zum Zitat Ali-Von Laue C, Zoschke C, Do N et al (2014) Improving topical non-melanoma skin cancer treatment: in vitro efficacy of a novel guanosine-analog phosphonate. Skin Pharmacol Physiol 27:173–180CrossRefPubMed Ali-Von Laue C, Zoschke C, Do N et al (2014) Improving topical non-melanoma skin cancer treatment: in vitro efficacy of a novel guanosine-analog phosphonate. Skin Pharmacol Physiol 27:173–180CrossRefPubMed
3.
Zurück zum Zitat Cadau S, Leoty-Okombi S, Pain S et al (2015) In vitro glycation of an endothelialized and innervated tissue-engineered skin to screen anti-AGE molecules. Biomaterials 51:216–225CrossRefPubMed Cadau S, Leoty-Okombi S, Pain S et al (2015) In vitro glycation of an endothelialized and innervated tissue-engineered skin to screen anti-AGE molecules. Biomaterials 51:216–225CrossRefPubMed
4.
Zurück zum Zitat Callaghan TM, Wilhelm KP (2008) 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 30:323–332CrossRefPubMed Callaghan TM, Wilhelm KP (2008) 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 30:323–332CrossRefPubMed
5.
Zurück zum Zitat Capell BC, Tlougan BE, Orlow SJ (2009) From the rarest to the most common: insights from progeroid syndromes into skin cancer and aging. J Invest Dermatol 129:2340–2350CrossRefPubMed Capell BC, Tlougan BE, Orlow SJ (2009) From the rarest to the most common: insights from progeroid syndromes into skin cancer and aging. J Invest Dermatol 129:2340–2350CrossRefPubMed
6.
Zurück zum Zitat Chi W, Wu E, Morgan BA (2013) Dermal papilla cell number specifies hair size, shape and cycling and its reduction causes follicular decline. Development 140:1676–1683PubMedCentralCrossRefPubMed Chi W, Wu E, Morgan BA (2013) Dermal papilla cell number specifies hair size, shape and cycling and its reduction causes follicular decline. Development 140:1676–1683PubMedCentralCrossRefPubMed
7.
Zurück zum Zitat Debusk FL (1972) The Hutchinson-Gilford progeria syndrome. Report of 4 cases and review of the literature. J Pediatr 80:697–724CrossRefPubMed Debusk FL (1972) The Hutchinson-Gilford progeria syndrome. Report of 4 cases and review of the literature. J Pediatr 80:697–724CrossRefPubMed
8.
Zurück zum Zitat Diekmann J, Alili L, Scholz O et al (2015) A three-dimensional skin equivalent reflecting some aspects of in-vivo aged skin. Exp Dermatol. doi:10.1111/exd.12866 Diekmann J, Alili L, Scholz O et al (2015) A three-dimensional skin equivalent reflecting some aspects of in-vivo aged skin. Exp Dermatol. doi:10.​1111/​exd.​12866
9.
Zurück zum Zitat Dierick JF, Eliaers F, Remacle J et al (2002) Stress-induced premature senescence and replicative senescence are different phenotypes, proteomic evidence. Biochem Pharmacol 64:1011–1017CrossRefPubMed Dierick JF, Eliaers F, Remacle J et al (2002) Stress-induced premature senescence and replicative senescence are different phenotypes, proteomic evidence. Biochem Pharmacol 64:1011–1017CrossRefPubMed
10.
Zurück zum Zitat Dimri GP, Lee X, Basile G et al (1995) A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci U S A 92:9363–9367PubMedCentralCrossRefPubMed Dimri GP, Lee X, Basile G et al (1995) A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci U S A 92:9363–9367PubMedCentralCrossRefPubMed
11.
Zurück zum Zitat Dos Santos M, Metral E, Boher A et al (2015) In vitro 3-D model based on extending time of culture for studying chronological epidermis aging. Matrix Biol 47:85–97CrossRefPubMed Dos Santos M, Metral E, Boher A et al (2015) In vitro 3-D model based on extending time of culture for studying chronological epidermis aging. Matrix Biol 47:85–97CrossRefPubMed
12.
Zurück zum Zitat El-Domyati M, Attia S, Saleh F et al (2002) Intrinsic aging vs. photoaging: a comparative histopathological, immunohistochemical, and ultrastructural study of skin. Exp Dermatol 11:398–405CrossRefPubMed El-Domyati M, Attia S, Saleh F et al (2002) Intrinsic aging vs. photoaging: a comparative histopathological, immunohistochemical, and ultrastructural study of skin. Exp Dermatol 11:398–405CrossRefPubMed
13.
Zurück zum Zitat Eriksson M, Brown WT, Gordon LB et al (2003) Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature 423:293–298CrossRefPubMed Eriksson M, Brown WT, Gordon LB et al (2003) Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature 423:293–298CrossRefPubMed
14.
Zurück zum Zitat Freund A, Orjalo AV, Desprez PY et al (2010) Inflammatory networks during cellular senescence: causes and consequences. Trends Mol Med 16:238–246PubMedCentralCrossRefPubMed Freund A, Orjalo AV, Desprez PY et al (2010) Inflammatory networks during cellular senescence: causes and consequences. Trends Mol Med 16:238–246PubMedCentralCrossRefPubMed
15.
17.
Zurück zum Zitat Hayflick L (1965) The limited in vitro lifetime of human diploid cell strains. Exp Cell Res 37:614–636CrossRefPubMed Hayflick L (1965) The limited in vitro lifetime of human diploid cell strains. Exp Cell Res 37:614–636CrossRefPubMed
18.
Zurück zum Zitat Janson D, Rietveld M, Willemze R et al (2013) Effects of serially passaged fibroblasts on dermal and epidermal morphogenesis in human skin equivalents. Biogerontology 14:131–140CrossRefPubMed Janson D, Rietveld M, Willemze R et al (2013) Effects of serially passaged fibroblasts on dermal and epidermal morphogenesis in human skin equivalents. Biogerontology 14:131–140CrossRefPubMed
19.
Zurück zum Zitat Kligman LH (1989) Photoaging. Manifestations, prevention, and treatment. Clin Geriatr Med 5:235–251PubMed Kligman LH (1989) Photoaging. Manifestations, prevention, and treatment. Clin Geriatr Med 5:235–251PubMed
20.
Zurück zum Zitat Kuro-O M, Matsumura Y, Aizawa H et al (1997) Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 390:45–51CrossRefPubMed Kuro-O M, Matsumura Y, Aizawa H et al (1997) Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 390:45–51CrossRefPubMed
21.
Zurück zum Zitat Lock-Andersen J, Therkildsen P, De Fine Olivarius F et al (1997) Epidermal thickness, skin pigmentation and constitutive photosensitivity. Photodermatol Photoimmunol Photomed 13:153–158CrossRefPubMed Lock-Andersen J, Therkildsen P, De Fine Olivarius F et al (1997) Epidermal thickness, skin pigmentation and constitutive photosensitivity. Photodermatol Photoimmunol Photomed 13:153–158CrossRefPubMed
22.
Zurück zum Zitat Löwenau L, Weindl G, Schäfer-Korting M (2013) A three-dimensional epidermis model reconstructed from UVB-irradiated keratinocytes mimics premature ageing in human skin. J Invest Dermatol 133:S215 Löwenau L, Weindl G, Schäfer-Korting M (2013) A three-dimensional epidermis model reconstructed from UVB-irradiated keratinocytes mimics premature ageing in human skin. J Invest Dermatol 133:S215
23.
Zurück zum Zitat Luebberding S, Krueger N, Kerscher M (2013) Skin physiology in men and women: in vivo evaluation of 300 people including TEWL, SC hydration, sebum content and skin surface pH. Int J Cosmet Sci 35:477–483CrossRefPubMed Luebberding S, Krueger N, Kerscher M (2013) Skin physiology in men and women: in vivo evaluation of 300 people including TEWL, SC hydration, sebum content and skin surface pH. Int J Cosmet Sci 35:477–483CrossRefPubMed
24.
Zurück zum Zitat Makrantonaki E, Zouboulis CC (2007) Molecular mechanisms of skin aging: state of the art. Ann N Y Acad Sci 1119:40–50CrossRefPubMed Makrantonaki E, Zouboulis CC (2007) Molecular mechanisms of skin aging: state of the art. Ann N Y Acad Sci 1119:40–50CrossRefPubMed
25.
Zurück zum Zitat Makrantonaki E, Adjaye J, Herwig R et al (2006) Age-specific hormonal decline is accompanied by transcriptional changes in human sebocytes in vitro. Aging Cell 5:331–344CrossRefPubMed Makrantonaki E, Adjaye J, Herwig R et al (2006) Age-specific hormonal decline is accompanied by transcriptional changes in human sebocytes in vitro. Aging Cell 5:331–344CrossRefPubMed
26.
Zurück zum Zitat Makrantonaki E, Brink TC, Zampeli V et al (2012) Identification of biomarkers of human skin ageing in both genders. Wnt signalling – a label of skin ageing? PLoS One 7:e50393PubMedCentralCrossRefPubMed Makrantonaki E, Brink TC, Zampeli V et al (2012) Identification of biomarkers of human skin ageing in both genders. Wnt signalling – a label of skin ageing? PLoS One 7:e50393PubMedCentralCrossRefPubMed
27.
Zurück zum Zitat Mcclintock D, Ratner D, Lokuge M et al (2007) The mutant form of lamin A that causes Hutchinson-Gilford progeria is a biomarker of cellular aging in human skin. PLoS One 2:e1269PubMedCentralCrossRefPubMed Mcclintock D, Ratner D, Lokuge M et al (2007) The mutant form of lamin A that causes Hutchinson-Gilford progeria is a biomarker of cellular aging in human skin. PLoS One 2:e1269PubMedCentralCrossRefPubMed
28.
29.
Zurück zum Zitat Moragas A, Castells C, Sans M (1993) Mathematical morphologic analysis of aging-related epidermal changes. Anal Quant Cytol Histol 15:75–82PubMed Moragas A, Castells C, Sans M (1993) Mathematical morphologic analysis of aging-related epidermal changes. Anal Quant Cytol Histol 15:75–82PubMed
30.
Zurück zum Zitat Nikolakis G, Makrantonaki E, Zouboulis CC (2013) Skin mirrors human aging. Horm Mol Biol Clin Investig 16:13–28PubMed Nikolakis G, Makrantonaki E, Zouboulis CC (2013) Skin mirrors human aging. Horm Mol Biol Clin Investig 16:13–28PubMed
31.
Zurück zum Zitat Nikolakis G, Seltmann H, Hossini AM et al (2015) Ex vivo human skin and SZ95 sebocytes exhibit a homoeostatic interaction in a novel coculture contact model. Exp Dermatol 24:497–502CrossRefPubMed Nikolakis G, Seltmann H, Hossini AM et al (2015) Ex vivo human skin and SZ95 sebocytes exhibit a homoeostatic interaction in a novel coculture contact model. Exp Dermatol 24:497–502CrossRefPubMed
32.
Zurück zum Zitat Ravelojaona V, Robert AM, Robert L (2009) 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 48:151–154CrossRefPubMed Ravelojaona V, Robert AM, Robert L (2009) 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 48:151–154CrossRefPubMed
33.
Zurück zum Zitat Rodier F, Munoz DP, Teachenor R et al (2011) DNA-SCARS: distinct nuclear structures that sustain damage-induced senescence growth arrest and inflammatory cytokine secretion. J Cell Sci 124:68–81PubMedCentralCrossRefPubMed Rodier F, Munoz DP, Teachenor R et al (2011) DNA-SCARS: distinct nuclear structures that sustain damage-induced senescence growth arrest and inflammatory cytokine secretion. J Cell Sci 124:68–81PubMedCentralCrossRefPubMed
34.
Zurück zum Zitat Rosengardten Y, Mckenna T, Grochova D et al (2011) Stem cell depletion in Hutchinson-Gilford progeria syndrome. Aging Cell 10:1011–1020CrossRefPubMed Rosengardten Y, Mckenna T, Grochova D et al (2011) Stem cell depletion in Hutchinson-Gilford progeria syndrome. Aging Cell 10:1011–1020CrossRefPubMed
35.
Zurück zum Zitat Schäfer-Korting M, Bock U, Diembeck W et al (2008) The use of reconstructed human epidermis for skin absorption testing: results of the validation study. Altern Lab Anim 36:161–187PubMed Schäfer-Korting M, Bock U, Diembeck W et al (2008) The use of reconstructed human epidermis for skin absorption testing: results of the validation study. Altern Lab Anim 36:161–187PubMed
36.
Zurück zum Zitat Seiberg M (2013) Age-induced hair greying – the multiple effects of oxidative stress. Int J Cosmet Sci 35:532–538CrossRefPubMed Seiberg M (2013) Age-induced hair greying – the multiple effects of oxidative stress. Int J Cosmet Sci 35:532–538CrossRefPubMed
37.
Zurück zum Zitat Simić-Krstić JB, Kalauzi AJ, Ribar SN et al (2014) Electrical properties of human skin as aging biomarkers. Exp Gerontol 57:163–167CrossRefPubMed Simić-Krstić JB, Kalauzi AJ, Ribar SN et al (2014) Electrical properties of human skin as aging biomarkers. Exp Gerontol 57:163–167CrossRefPubMed
38.
Zurück zum Zitat Südel KM, Venzke K, Mielke H et al (2005) Novel aspects of intrinsic and extrinsic aging of human skin: beneficial effects of soy extract. Photochem Photobiol 81:581–587CrossRefPubMed Südel KM, Venzke K, Mielke H et al (2005) Novel aspects of intrinsic and extrinsic aging of human skin: beneficial effects of soy extract. Photochem Photobiol 81:581–587CrossRefPubMed
39.
Zurück zum Zitat Tigges J, Krutmann J, Fritsche E et al (2014) The hallmarks of fibroblast ageing. Mech Ageing Dev 138:26–44CrossRefPubMed Tigges J, Krutmann J, Fritsche E et al (2014) The hallmarks of fibroblast ageing. Mech Ageing Dev 138:26–44CrossRefPubMed
40.
Zurück zum Zitat Waller JM, Maibach HI (2005) Age and skin structure and function, a quantitative approach (I): blood flow, pH, thickness, and ultrasound echogenicity. Skin Res Technol 11:221–235CrossRefPubMed Waller JM, Maibach HI (2005) Age and skin structure and function, a quantitative approach (I): blood flow, pH, thickness, and ultrasound echogenicity. Skin Res Technol 11:221–235CrossRefPubMed
41.
Zurück zum Zitat Waller JM, Maibach HI (2006) Age and skin structure and function, a quantitative approach (II): protein, glycosaminoglycan, water, and lipid content and structure. Skin Res Technol 12:145–154CrossRefPubMed Waller JM, Maibach HI (2006) Age and skin structure and function, a quantitative approach (II): protein, glycosaminoglycan, water, and lipid content and structure. Skin Res Technol 12:145–154CrossRefPubMed
42.
Zurück zum Zitat Xia W, Quan T, Hammerberg C et al (2015) A mouse model of skin aging: fragmentation of dermal collagen fibrils and reduced fibroblast spreading due to expression of human matrix metalloproteinase-1. J Dermatol Sci 78:79–82CrossRefPubMed Xia W, Quan T, Hammerberg C et al (2015) A mouse model of skin aging: fragmentation of dermal collagen fibrils and reduced fibroblast spreading due to expression of human matrix metalloproteinase-1. J Dermatol Sci 78:79–82CrossRefPubMed
43.
Zurück zum Zitat Yang YC, Fu HC, Wu CY et al (2013) Androgen receptor accelerates premature senescence of human dermal papilla cells in association with DNA damage. PLoS One 8:e79434PubMedCentralCrossRefPubMed Yang YC, Fu HC, Wu CY et al (2013) Androgen receptor accelerates premature senescence of human dermal papilla cells in association with DNA damage. PLoS One 8:e79434PubMedCentralCrossRefPubMed
44.
Zurück zum Zitat Zoschke C, Schilrreff P, Romero EL et al (2015) Dendritic nanoparticles for cutaneous drug delivery – testing in human skin and reconstructed human skin. Curr Pharm Des 21:2784–2800CrossRefPubMed Zoschke C, Schilrreff P, Romero EL et al (2015) Dendritic nanoparticles for cutaneous drug delivery – testing in human skin and reconstructed human skin. Curr Pharm Des 21:2784–2800CrossRefPubMed
45.
Zurück zum Zitat Zouboulis CC, Chen W (2013) The sebaceous gland and its role as an endocrine organ. World Clin Dermatol 1(1):37–51 Zouboulis CC, Chen W (2013) The sebaceous gland and its role as an endocrine organ. World Clin Dermatol 1(1):37–51
46.
Zurück zum Zitat Zouboulis CC, Makrantonaki E (2011) Clinical aspects and molecular diagnostics of skin aging. Clin Dermatol 29:3–14CrossRefPubMed Zouboulis CC, Makrantonaki E (2011) Clinical aspects and molecular diagnostics of skin aging. Clin Dermatol 29:3–14CrossRefPubMed
47.
Zurück zum Zitat Zouboulis CC, Seltmann H, Neitzel H, Orfanos CE (1999) Establishment and characterization of an immortalized human sebaceous gland cell line (SZ95). J Invest Dermatol 113:1011–1020CrossRefPubMed Zouboulis CC, Seltmann H, Neitzel H, Orfanos CE (1999) Establishment and characterization of an immortalized human sebaceous gland cell line (SZ95). J Invest Dermatol 113:1011–1020CrossRefPubMed
Metadaten
Titel
Experimentelle Modelle humaner Hautalterung
verfasst von
G. Nikolakis
C. Zoschke
E. Makrantonaki
C. Hausmann
M. Schäfer-Korting
Prof. Dr. med. Prof. h.c. Dr. h.c. C. C. Zouboulis
Publikationsdatum
01.02.2016
Verlag
Springer Berlin Heidelberg
Schlagwort
Hautalterung
Erschienen in
Die Dermatologie / Ausgabe 2/2016
Print ISSN: 2731-7005
Elektronische ISSN: 2731-7013
DOI
https://doi.org/10.1007/s00105-015-3747-1

Weitere Artikel der Ausgabe 2/2016

Der Hautarzt 2/2016 Zur Ausgabe

Panorama Dermatologische Praxis

Panorama Dermatologische Praxis

Leitlinien kompakt für die Dermatologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Dermatologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.