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Aging of Stem Cells in Skin: What Is Driving the Aging Process?

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Book cover Stem Cell Aging: Mechanisms, Consequences, Rejuvenation

Abstract

Skin is a complex organ consisting of two very different tissue compartments, the epidermis and the dermis, which comprise cells of diverse origin and function. Establishing and maintaining the functionality of skin requires not only tightly regulated processes of maturation and differentiation of the individual cellular components but also extensive and well-coordinated interactions between those different compartments. As yet, this intricate interdependence is far from being disclosed to a satisfactory extent. Accordingly, our understanding for dysregulated conditions like skin aging is still largely insufficient. Despite the fact that skin aging is readily visible and morphologically well defined, the underlying molecular mechanisms driving that process are still a matter of debate as is the role of stem cells therein. Furthermore, the aging of skin is peculiar as it is not only driven endogenously but is largely accelerated and aggravated by external influences, mainly, UV radiation, what is reflected by the term “photoaging.” By foregrounding human skin, this chapter aims at compiling the present concepts of both intrinsic and extrinsic skin aging.

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References

  • Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Water P (2004) Molekularbiologie der Zelle, vol 4. Wiley-VCH Verlag GmbH, Weinheim

    Google Scholar 

  • Angel P, Szabowski A, Schorpp-Kistner M (2001) Function and regulation of AP-1 subunits in skin physiology and pathology. Oncogene 20(19):2413–2423. doi:10.1038/sj.onc.1204380

    CAS  PubMed  Google Scholar 

  • Ashworth JL, Murphy G, Rock MJ, Sherratt MJ, Shapiro SD, Shuttleworth CA, Kielty CM (1999) Fibrillin degradation by matrix metalloproteinases: implications for connective tissue remodelling. Biochem J 340(Pt 1):171–181

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ayouaz A, Raynaud C, Heride C, Revaud D, Sabatier L (2008) Telomeres: hallmarks of radiosensitivity. Biochimie 90(1):60–72. doi:10.1016/j.biochi.2007.09.011

    CAS  PubMed  Google Scholar 

  • Bailey AJ (2001) Molecular mechanisms of ageing in connective tissues. Mech Ageing Dev 122(7):735–755

    CAS  PubMed  Google Scholar 

  • Bailey AJ, Paul RG, Knott L (1998) Mechanisms of maturation and ageing of collagen. Mech Ageing Dev 106(1–2):1–56

    CAS  PubMed  Google Scholar 

  • Barrandon Y, Green H (1987) Three clonal types of keratinocyte with different capacities for multiplication. Proc Natl Acad Sci U S A 84(8):2302–2306

    CAS  PubMed Central  PubMed  Google Scholar 

  • Baumann L (2007) Skin ageing and its treatment. J Pathol 211(2):241–251. doi:10.1002/path.2098

    CAS  PubMed  Google Scholar 

  • Berneburg M, Gattermann N, Stege H, Grewe M, Vogelsang K, Ruzicka T, Krutmann J (1997) Chronically ultraviolet-exposed human skin shows a higher mutation frequency of mitochondrial DNA as compared to unexposed skin and the hematopoietic system. Photochem Photobiol 66(2):271–275

    CAS  PubMed  Google Scholar 

  • Berneburg M, Plettenberg H, Krutmann J (2000) Photoaging of human skin. Photodermatol Photoimmunol Photomed 16(6):239–244

    CAS  PubMed  Google Scholar 

  • Bernstein EF, Chen YQ, Kopp JB, Fisher L, Brown DB, Hahn PJ, Robey FA, Lakkakorpi J, Uitto J (1996a) Long-term sun exposure alters the collagen of the papillary dermis. Comparison of sun-protected and photoaged skin by northern analysis, immunohistochemical staining, and confocal laser scanning microscopy. J Am Acad Dermatol 34(2 Pt 1):209–218

    CAS  PubMed  Google Scholar 

  • Bernstein EF, Underhill CB, Hahn PJ, Brown DB, Uitto J (1996b) Chronic sun exposure alters both the content and distribution of dermal glycosaminoglycans. Br J Dermatol 135(2):255–262

    CAS  PubMed  Google Scholar 

  • Berton A, Godeau G, Emonard H, Baba K, Bellon P, Hornebeck W, Bellon G (2000) Analysis of the ex vivo specificity of human gelatinases A and B towards skin collagen and elastic fibers by computerized morphometry. Matrix Biol 19(2):139–148

    CAS  PubMed  Google Scholar 

  • Bhushan M, Cumberbatch M, Dearman RJ, Andrew SM, Kimber I, Griffiths CE (2002) Tumour necrosis factor-alpha-induced migration of human Langerhans cells: the influence of ageing. Br J Dermatol 146(1):32–40

    CAS  PubMed  Google Scholar 

  • Birkedal-Hansen H, Moore WG, Bodden MK, Windsor LJ, Birkedal-Hansen B, DeCarlo A, Engler JA (1993) Matrix metalloproteinases: a review. Crit Rev Oral Biol Med 4(2):197–250

    CAS  PubMed  Google Scholar 

  • Boehnke K, Falkowska-Hansen B, Stark HJ, Boukamp P (2012) Stem cells of the human epidermis and their niche: composition and function in epidermal regeneration and carcinogenesis. Carcinogenesis 33(7):1247–1258. doi:10.1093/carcin/bgs136

    CAS  PubMed  Google Scholar 

  • Bolognia JL, Braverman IM, Rousseau ME, Sarrel PM (1989) Skin changes in menopause. Maturitas 11(4):295–304

    CAS  PubMed  Google Scholar 

  • Borkowski TA, Letterio JJ, Farr AG, Udey MC (1996) A role for endogenous transforming growth factor beta 1 in Langerhans cell biology: the skin of transforming growth factor beta 1 null mice is devoid of epidermal Langerhans cells. J Exp Med 184(6):2417–2422

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bornstein P, Sage EH (2002) Matricellular proteins: extracellular modulators of cell function. Curr Opin Cell Biol 14(5):608–616

    CAS  PubMed  Google Scholar 

  • Bosset S, Bonnet-Duquennoy M, Barre P, Chalon A, Lazou K, Kurfurst R, Bonte F, Schnebert S, Disant F, Le Varlet B, Nicolas JF (2003) Decreased expression of keratinocyte beta1 integrins in chronically sun-exposed skin in vivo. Br J Dermatol 148(4):770–778

    CAS  PubMed  Google Scholar 

  • Branchet MC, Boisnic S, Frances C, Robert AM (1990) Skin thickness changes in normal aging skin. Gerontology 36(1):28–35

    CAS  PubMed  Google Scholar 

  • Breathnach AS, Wyllie LM (1964) Electron microscopy of melanocytes and melanosomes in freckled human epidermis. J Invest Dermatol 42:389–394

    CAS  PubMed  Google Scholar 

  • Brincat MP (2000) Hormone replacement therapy and the skin. Maturitas 35(2):107–117

    CAS  PubMed  Google Scholar 

  • Brohem CA, de Carvalho CM, Radoski CL, Santi FC, Baptista MC, Swinka BB, de A Urban C, de Araujo LR, Graf RM, Feferman IH, Lorencini M (2013) Comparison between fibroblasts and mesenchymal stem cells derived from dermal and adipose tissue. Int J Cosmet Sci 35(5):448–457. doi:10.1111/ics.12064

    CAS  PubMed  Google Scholar 

  • Camougrand N, Rigoulet M (2001) Aging and oxidative stress: studies of some genes involved both in aging and in response to oxidative stress. Respir Physiol 128(3):393–401

    CAS  PubMed  Google Scholar 

  • Campisi J (1996) Replicative senescence: an old lives’ tale? Cell 84(4):497–500

    CAS  PubMed  Google Scholar 

  • Charruyer A, Barland CO, Yue L, Wessendorf HB, Lu Y, Lawrence HJ, Mancianti ML, Ghadially R (2009) Transit-amplifying cell frequency and cell cycle kinetics are altered in aged epidermis. J Invest Dermatol 129(11):2574–2583. doi:10.1038/jid.2009.127

    CAS  PubMed  Google Scholar 

  • Chen VL, Fleischmajer R, Schwartz E, Palaia M, Timpl R (1986) Immunochemistry of elastotic material in sun-damaged skin. J Invest Dermatol 87(3):334–337

    CAS  PubMed  Google Scholar 

  • Chen FG, Zhang WJ, Bi D, Liu W, Wei X, Chen FF, Zhu L, Cui L, Cao Y (2007) Clonal analysis of nestin(−) vimentin(+) multipotent fibroblasts isolated from human dermis. J Cell Sci 120(Pt 16):2875–2883. doi:10.1242/jcs.03478

    CAS  PubMed  Google Scholar 

  • Chung JH, Kang S, Varani J, Lin J, Fisher GJ, Voorhees JJ (2000) Decreased extracellular-signal-regulated kinase and increased stress-activated MAP kinase activities in aged human skin in vivo. J Invest Dermatol 115(2):177–182. doi:10.1046/j.1523-1747.2000.00009.x

    CAS  PubMed  Google Scholar 

  • Commo S, Gaillard O, Bernard BA (2004) Human hair greying is linked to a specific depletion of hair follicle melanocytes affecting both the bulb and the outer root sheath. Br J Dermatol 150(3):435–443. doi:10.1046/j.1365-2133.2004.05787.x

    CAS  PubMed  Google Scholar 

  • Contet-Audonneau JL, Jeanmaire C, Pauly G (1999) A histological study of human wrinkle structures: comparison between sun-exposed areas of the face, with or without wrinkles, and sun-protected areas. Br J Dermatol 140(6):1038–1047

    CAS  PubMed  Google Scholar 

  • Craven NM, Watson RE, Jones CJ, Shuttleworth CA, Kielty CM, Griffiths CE (1997) Clinical features of photodamaged human skin are associated with a reduction in collagen VII. Br J Dermatol 137(3):344–350

    CAS  PubMed  Google Scholar 

  • Crigler L, Kazhanie A, Yoon TJ, Zakhari J, Anders J, Taylor B, Virador VM (2007) Isolation of a mesenchymal cell population from murine dermis that contains progenitors of multiple cell lineages. Faseb J 21(9):2050–2063. doi:10.1096/fj.06-5880com

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cristofalo VJ, Lorenzini A, Allen RG, Torres C, Tresini M (2004) Replicative senescence: a critical review. Mech Ageing Dev 125(10–11):827–848. doi:10.1016/j.mad.2004.07.010

    CAS  PubMed  Google Scholar 

  • d’Adda di Fagagna F, Reaper PM, Clay-Farrace L, Fiegler H, Carr P, Von Zglinicki T, Saretzki G, Carter NP, Jackson SP (2003) A DNA damage checkpoint response in telomere-initiated senescence. Nature 426(6963):194–198. doi:10.1038/nature02118

    PubMed  Google Scholar 

  • da Silva Meirelles L, Caplan AI, Nardi NB (2008) In search of the in vivo identity of mesenchymal stem cells. Stem Cells 26(9):2287–2299. doi:10.1634/stemcells.2007-1122

    PubMed  Google Scholar 

  • Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, Medrano EE, Linskens M, Rubelj I, Pereira-Smith O 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(20):9363–9367

    CAS  PubMed Central  PubMed  Google Scholar 

  • Doles J, Keyes WM (2013) Epidermal stem cells undergo age-associated changes. Aging (Milano) 5(1):1–2

    Google Scholar 

  • Dyce PW, Zhu H, Craig J, Li J (2004) Stem cells with multilineage potential derived from porcine skin. Biochem Biophys Res Commun 316(3):651–658. doi:10.1016/j.bbrc.2004.02.093

    CAS  PubMed  Google Scholar 

  • El-Domyati M, Attia S, Saleh F, Brown D, Birk DE, Gasparro F, Ahmad H, Uitto J (2002) Intrinsic aging vs. photoaging: a comparative histopathological, immunohistochemical, and ultrastructural study of skin. Exp Dermatol 11(5):398–405

    CAS  PubMed  Google Scholar 

  • Engelke M, Jensen JM, Ekanayake-Mudiyanselage S, Proksch E (1997) Effects of xerosis and ageing on epidermal proliferation and differentiation. Br J Dermatol 137(2):219–225

    CAS  PubMed  Google Scholar 

  • Fenske NA, Lober CW (1986) Structural and functional changes of normal aging skin. J Am Acad Dermatol 15(4 Pt 1):571–585

    CAS  PubMed  Google Scholar 

  • Fernandes KJ, Kobayashi NR, Gallagher CJ, Barnabe-Heider F, Aumont A, Kaplan DR, Miller FD (2006) Analysis of the neurogenic potential of multipotent skin-derived precursors. Exp Neurol 201(1):32–48. doi:10.1016/j.expneurol.2006.03.018

    PubMed  Google Scholar 

  • Fisher GJ, Datta SC, Talwar HS, Wang ZQ, Varani J, Kang S, Voorhees JJ (1996) Molecular basis of sun-induced premature skin ageing and retinoid antagonism. Nature 379(6563):335–339. doi:10.1038/379335a0

    CAS  PubMed  Google Scholar 

  • Fisher GJ, Talwar HS, Lin J, Lin P, McPhillips F, Wang Z, Li X, Wan Y, Kang S, Voorhees JJ (1998) Retinoic acid inhibits induction of c-Jun protein by ultraviolet radiation that occurs subsequent to activation of mitogen-activated protein kinase pathways in human skin in vivo. J Clin Invest 101(6):1432–1440. doi:10.1172/JCI2153

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fisher GJ, Kang S, Varani J, Bata-Csorgo Z, Wan Y, Datta S, Voorhees JJ (2002) Mechanisms of photoaging and chronological skin aging. Arch Dermatol 138(11):1462–1470

    CAS  PubMed  Google Scholar 

  • Fisher GJ, Varani J, Voorhees JJ (2008) Looking older: fibroblast collapse and therapeutic implications. Arch Dermatol 144(5):666–672. doi:10.1001/archderm.144.5.666

    PubMed Central  PubMed  Google Scholar 

  • Fisher GJ, Quan T, Purohit T, Shao Y, Cho MK, He T, Varani J, Kang S, Voorhees JJ (2009) Collagen fragmentation promotes oxidative stress and elevates matrix metalloproteinase-1 in fibroblasts in aged human skin. Am J Pathol 174(1):101–114. doi:10.2353/ajpath.2009.080599

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fleischmajer R, Perlish JS, Bashey RI (1972) Human dermal glycosaminoglycans and aging. Biochim Biophys Acta 279(2):265–275

    CAS  PubMed  Google Scholar 

  • Frances C, Branchet MC, Boisnic S, Lesty CL, Robert L (1990) Elastic fibers in normal human skin. Variations with age: a morphometric analysis. Arch Gerontol Geriatr 10(1):57–67

    CAS  PubMed  Google Scholar 

  • Fritsch P (2009) Dermatologie und Venerologie für das Studium. Springer Medizin Verlag, Heidelberg

    Google Scholar 

  • Gago N, Perez-Lopez V, Sanz-Jaka JP, Cormenzana P, Eizaguirre I, Bernad A, Izeta A (2009) Age-dependent depletion of human skin-derived progenitor cells. Stem Cells 27(5):1164–1172. doi:10.1002/stem.27

    CAS  PubMed  Google Scholar 

  • Gallico GG 3rd, O’Connor NE, Compton CC, Kehinde O, Green H (1984) Permanent coverage of large burn wounds with autologous cultured human epithelium. N Engl J Med 311(7):448–451. doi:10.1056/NEJM198408163110706

    PubMed  Google Scholar 

  • Garrone R, Lethias C, Le Guellec D (1997) Distribution of minor collagens during skin development. Microsc Res Tech 38(4):407–412. doi:10.1002/(SICI)1097-0029(19970815)38:4<407::AID-JEMT8>3.0.CO;2-F

    CAS  PubMed  Google Scholar 

  • Ghersetich I, Lotti T, Campanile G, Grappone C, Dini G (1994) Hyaluronic acid in cutaneous intrinsic aging. Int J Dermatol 33(2):119–122

    CAS  PubMed  Google Scholar 

  • Ghigo C, Mondor I, Jorquera A, Nowak J, Wienert S, Zahner SP, Clausen BE, Luche H, Malissen B, Klauschen F, Bajenoff M (2013) Multicolor fate mapping of Langerhans cell homeostasis. J Exp Med 210(9):1657–1664. doi:10.1084/jem.20130403

    CAS  PubMed Central  PubMed  Google Scholar 

  • Giacomoni PU, Declercq L, Hellemans L, Maes D (2000) Aging of human skin: review of a mechanistic model and first experimental data. IUBMB Life 49(4):259–263. doi:10.1080/15216540050033104

    CAS  PubMed  Google Scholar 

  • Giangreco A, Qin M, Pintar JE, Watt FM (2008) Epidermal stem cells are retained in vivo throughout skin aging. Aging Cell 7(2):250–259. doi:10.1111/j.1474-9726.2008.00372.x

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gilchrest BA, Blog FB, Szabo G (1979) Effects of aging and chronic sun exposure on melanocytes in human skin. J Invest Dermatol 73(2):141–143

    CAS  PubMed  Google Scholar 

  • Gingras M, Champigny MF, Berthod F (2007) Differentiation of human adult skin-derived neuronal precursors into mature neurons. J Cell Physiol 210(2):498–506. doi:10.1002/jcp.20889

    CAS  PubMed  Google Scholar 

  • Gniadecka M, Nielsen OF, Wessel S, Heidenheim M, Christensen DH, Wulf HC (1998) Water and protein structure in photoaged and chronically aged skin. J Invest Dermatol 111(6):1129–1133. doi:10.1046/j.1523-1747.1998.00430.x

    CAS  PubMed  Google Scholar 

  • Grewe M (2001) Chronological ageing and photoageing of dendritic cells. Clin Exp Dermatol 26(7):608–612

    CAS  PubMed  Google Scholar 

  • Griffiths CE, Russman AN, Majmudar G, Singer RS, Hamilton TA, Voorhees JJ (1993) Restoration of collagen formation in photodamaged human skin by tretinoin (retinoic acid). N Engl J Med 329(8):530–535. doi:10.1056/NEJM199308193290803

    CAS  PubMed  Google Scholar 

  • Grove GL, Kligman AM (1983) Age-associated changes in human epidermal cell renewal. J Gerontol 38(2):137–142

    CAS  PubMed  Google Scholar 

  • Gundermann S, Stark HJ, Kollar J, Busch H, Börries M, Weber S, Bickenbach JR, Boukamp P (2015) TGFβ-dependent transdifferentiation of human dermal fibroblasts towards a chondrocyte phenotype is causally related to photoaging. Submitted

    Google Scholar 

  • Gunin AG, Kornilova NK, Petrov VV, Vasil’eva OV (2011a) Age-related changes in the number and proliferation of fibroblasts in the human skin. Adv Gerontol 24(1):43–47

    CAS  PubMed  Google Scholar 

  • Gunin AG, Kornilova NK, Vasilieva OV, Petrov VV (2011b) Age-related changes in proliferation, the numbers of mast cells, eosinophils, and cd45-positive cells in human dermis. J Gerontol A Biol Sci Med Sci 66(4):385–392. doi:10.1093/gerona/glq205

    PubMed  Google Scholar 

  • Hacker C, Kirsch RD, Ju XS, Hieronymus T, Gust TC, Kuhl C, Jorgas T, Kurz SM, Rose-John S, Yokota Y, Zenke M (2003) Transcriptional profiling identifies Id2 function in dendritic cell development. Nat Immunol 4(4):380–386. doi:10.1038/ni903

    CAS  PubMed  Google Scholar 

  • Hanson KM, Simon JD (1998) Epidermal trans-urocanic acid and the UV-A-induced photoaging of the skin. Proc Natl Acad Sci U S A 95(18):10576–10578

    CAS  PubMed Central  PubMed  Google Scholar 

  • Harle-Bachor C, Boukamp P (1996) Telomerase activity in the regenerative basal layer of the epidermis inhuman skin and in immortal and carcinoma-derived skin keratinocytes. Proc Natl Acad Sci U S A 93(13):6476–6481

    CAS  PubMed Central  PubMed  Google Scholar 

  • Harley CB, Futcher AB, Greider CW (1990) Telomeres shorten during ageing of human fibroblasts. Nature 345(6274):458–460. doi:10.1038/345458a0

    CAS  PubMed  Google Scholar 

  • Hayflick L (1965) The limited in vitro lifetime of human diploid cell strains. Exp Cell Res 37:614–636

    CAS  PubMed  Google Scholar 

  • Hayflick L, Moorhead PS (1961) The serial cultivation of human diploid cell strains. Exp Cell Res 25:585–621

    CAS  PubMed  Google Scholar 

  • Herbig U, Jobling WA, Chen BP, Chen DJ, Sedivy JM (2004) Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21(CIP1), but not p16(INK4a). Mol Cell 14(4):501–513

    CAS  PubMed  Google Scholar 

  • Hieronymus T, Zenke M, Baek JH, Seré K (2014) The clash of Langerhans cell homeostasis in skin: Should I stay or should I go? Semin Cell Dev Biol. pii: S1084-9521(14)00021-4. doi:10.1016/j.semcdb.2014.02.009. [Epub ahead of print] Review.

  • Hoeffel G, Wang Y, Greter M, See P, Teo P, Malleret B, Leboeuf M, Low D, Oller G, Almeida F, Choy SH, Grisotto M, Renia L, Conway SJ, Stanley ER, Chan JK, Ng LG, Samokhvalov IM, Merad M, Ginhoux F (2012) Adult Langerhans cells derive predominantly from embryonic fetal liver monocytes with a minor contribution of yolk sac-derived macrophages. J Exp Med 209(6):1167–1181. doi:10.1084/jem.20120340

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hoetzenecker W, Ecker R, Kopp T, Stuetz A, Stingl G, Elbe-Burger A (2005) Pimecrolimus leads to an apoptosis-induced depletion of T cells but not Langerhans cells in patients with atopic dermatitis. J Allergy Clin Immunol 115(6):1276–1283. doi:10.1016/j.jaci.2005.02.011

    CAS  PubMed  Google Scholar 

  • Hoogduijn MJ, Gorjup E, Genever PG (2006) Comparative characterization of hair follicle dermal stem cells and bone marrow mesenchymal stem cells. Stem Cells Dev 15(1):49–60. doi:10.1089/scd.2006.15.49

    CAS  PubMed  Google Scholar 

  • Hughes MC, Bredoux C, Salas F, Lombard D, Strutton GM, Fourtanier A, Green AC (2011) Comparison of histological measures of skin photoaging. Dermatology 223(2):140–151. doi:10.1159/000332425

    CAS  PubMed  Google Scholar 

  • Imokawa G (2008) Recent advances in characterizing biological mechanisms underlying UV-induced wrinkles: a pivotal role of fibroblast-derived elastase. Arch Dermatol Res 300(Suppl 1):S7–S20. doi:10.1007/s00403-007-0798-x

    CAS  PubMed  Google Scholar 

  • Ingber DE, Wang N, Stamenovic D (2014) Tensegrity, cellular biophysics, and the mechanics of living systems. Rep Prog Phys 77(4):046603. doi:10.1088/0034-4885/77/4/046603

    PubMed Central  PubMed  Google Scholar 

  • Jackson RL, Greiwe JS, Schwen RJ (2011) Ageing skin: oestrogen receptor beta agonists offer an approach to change the outcome. Exp Dermatol 20(11):879–882. doi:10.1111/j.1600-0625.2011.01362.x

    CAS  PubMed  Google Scholar 

  • Jahoda CA, Whitehouse J, Reynolds AJ, Hole N (2003) Hair follicle dermal cells differentiate into adipogenic and osteogenic lineages. Exp Dermatol 12(6):849–859

    PubMed  Google Scholar 

  • Jenkins G (2002) Molecular mechanisms of skin ageing. Mech Ageing Dev 123(7):801–810

    CAS  PubMed  Google Scholar 

  • Johnson R, Jackson IJ (1992) Light is a dominant mouse mutation resulting in premature cell death. Nat Genet 1(3):226–229. doi:10.1038/ng0692-226

    CAS  PubMed  Google Scholar 

  • Junker JP, Sommar P, Skog M, Johnson H, Kratz G (2010) Adipogenic, chondrogenic and osteogenic differentiation of clonally derived human dermal fibroblasts. Cells Tissues Organs 191(2):105–118. doi:10.1159/000232157

    PubMed  Google Scholar 

  • Kanitakis J (2002) Anatomy, histology and immunohistochemistry of normal human skin. Eur J Dermatol 12(4):390–399; quiz 400–401

    PubMed  Google Scholar 

  • Kel JM, Girard-Madoux MJ, Reizis B, Clausen BE (2010) TGF-beta is required to maintain the pool of immature Langerhans cells in the epidermis. J Immunol 185(6):3248–3255. doi:10.4049/jimmunol.1000981

    CAS  PubMed  Google Scholar 

  • Kessler D, Dethlefsen S, Haase I, Plomann M, Hirche F, Krieg T, Eckes B (2001) Fibroblasts in mechanically stressed collagen lattices assume a “synthetic” phenotype. J Biol Chem 276(39):36575–36585. doi:10.1074/jbc.M101602200

    CAS  PubMed  Google Scholar 

  • Kligman AM (1969) Early destructive effect of sunlight on human skin. JAMA 210(13):2377–2380

    CAS  PubMed  Google Scholar 

  • Klotz LO, Pellieux C, Briviba K, Pierlot C, Aubry JM, Sies H (1999) Mitogen-activated protein kinase (p38-, JNK-, ERK-) activation pattern induced by extracellular and intracellular singlet oxygen and UVA. Eur J Biochem 260(3):917–922

    CAS  PubMed  Google Scholar 

  • Kohl E, Landthaler M, Szeimies RM (2009) Skin aging. Hautarzt 60(11):917–933. doi:10.1007/s00105-009-1790-5; quiz 934

    CAS  PubMed  Google Scholar 

  • Kohl E, Steinbauer J, Landthaler M, Szeimies RM (2011) Skin ageing. J Eur Acad Dermatol Venereol 25(8):873–884. doi:10.1111/j.1468-3083.2010.03963.x

    CAS  PubMed  Google Scholar 

  • Krunic D, Moshir S, Greulich-Bode KM, Figueroa R, Cerezo A, Stammer H, Stark HJ, Gray SG, Nielsen KV, Hartschuh W, Boukamp P (2009) Tissue context-activated telomerase in human epidermis correlates with little age-dependent telomere loss. Biochim Biophys Acta 1792(4):297–308. doi:10.1016/j.bbadis.2009.02.005

    CAS  PubMed  Google Scholar 

  • Krutmann J (2003) Premature skin aging by ultraviolet radiation and other environmental hazards. The molecular basis. Hautarzt 54(9):809–817. doi:10.1007/s00105-003-0575-5

    CAS  PubMed  Google Scholar 

  • Krutmann J (2011) How the sun ages our skin. The dermis as the driving force. Hautarzt 62(8):588–590. doi:10.1007/s00105-011-2132-y

    CAS  PubMed  Google Scholar 

  • Krutmann J, Diepgen T, Billmann-Krutmann C (2008) Hautalterung, vol 2. Springer Medizin Verlag, Heidelberg

    Google Scholar 

  • Lako M, Armstrong L, Cairns PM, Harris S, Hole N, Jahoda CA (2002) Hair follicle dermal cells repopulate the mouse haematopoietic system. J Cell Sci 115(Pt 20):3967–3974

    CAS  PubMed  Google Scholar 

  • Langton AK, Sherratt MJ, Griffiths CE, Watson RE (2010) A new wrinkle on old skin: the role of elastic fibres in skin ageing. Int J Cosmet Sci. doi:10.1111/j.1468-2494.2010.00574.x

    PubMed  Google Scholar 

  • Lavker RM (1979) Structural alterations in exposed and unexposed aged skin. J Invest Dermatol 73(1):59–66

    CAS  PubMed  Google Scholar 

  • Lavker RM, Kligman AM (1988) Chronic heliodermatitis: a morphologic evaluation of chronic actinic dermal damage with emphasis on the role of mast cells. J Invest Dermatol 90(3):325–330

    CAS  PubMed  Google Scholar 

  • Lecardonnel J, Deshayes N, Genty G, Parent N, Bernard BA, Rathman-Josserand M, Paris M (2013) Ageing and colony-forming efficiency of human hair follicle keratinocytes. Exp Dermatol 22(9):604–606. doi:10.1111/exd.12204

    CAS  PubMed  Google Scholar 

  • Leufke C, Leykauf J, Krunic D, Jauch A, Holtgreve-Grez H, Bohm-Steuer B, Brocker EB, Mauch C, Utikal J, Hartschuh W, Purdie KJ, Boukamp P (2013) The telomere profile distinguishes two classes of genetically distinct cutaneous squamous cell carcinomas. Oncogene. doi:10.1038/onc.2013.323

    PubMed  Google Scholar 

  • Levy MZ, Allsopp RC, Futcher AB, Greider CW, Harley CB (1992) Telomere end-replication problem and cell aging. J Mol Biol 225(4):951–960

    CAS  PubMed  Google Scholar 

  • Liang L, Chinnathambi S, Stern M, Tomanek-Chalkley A, Manuel TD, Bickenbach JR (2004) As epidermal stem cells age they do not substantially change their characteristics. J Investig Dermatol Symp Proc 9(3):229–237. doi:10.1111/j.1087-0024.2004.09309.x

    CAS  PubMed  Google Scholar 

  • Lindsey J, McGill NI, Lindsey LA, Green DK, Cooke HJ (1991) In vivo loss of telomeric repeats with age in humans. Mutat Res 256(1):45–48

    CAS  PubMed  Google Scholar 

  • Lock-Andersen J, Therkildsen P, de Fine Olivarius F, Gniadecka M, Dahlstrom K, Poulsen T, Wulf HC (1997) Epidermal thickness, skin pigmentation and constitutive photosensitivity. Photodermatol Photoimmunol Photomed 13(4):153–158

    CAS  PubMed  Google Scholar 

  • Löffler G, Petrides PE, Heinrich PC (2007) Binde- und Stützgewebe. In: Deutzmann R, Bruckner-Tuderman L, Bruckner P (eds) Biochemie und Pathobiochemie, vol 8. Springer Medizin Verlag, Heidelberg, pp 461–469

    Google Scholar 

  • Lombard DB, Chua KF, Mostoslavsky R, Franco S, Gostissa M, Alt FW (2005) DNA repair, genome stability, and aging. Cell 120(4):497–512. doi:10.1016/j.cell.2005.01.028

    CAS  PubMed  Google Scholar 

  • Lorenz K, Sicker M, Schmelzer E, Rupf T, Salvetter J, Schulz-Siegmund M, Bader A (2008) Multilineage differentiation potential of human dermal skin-derived fibroblasts. Exp Dermatol 17(11):925–932. doi:10.1111/j.1600-0625.2008.00724.x

    CAS  PubMed  Google Scholar 

  • Lovell CR, Smolenski KA, Duance VC, Light ND, Young S, Dyson M (1987) Type I and III collagen content and fibre distribution in normal human skin during ageing. Br J Dermatol 117(4):419–428

    CAS  PubMed  Google Scholar 

  • Lysy PA, Smets F, Sibille C, Najimi M, Sokal EM (2007) Human skin fibroblasts: From mesodermal to hepatocyte-like differentiation. Hepatology 46(5):1574–1585. doi:10.1002/hep.28139

    CAS  PubMed  Google Scholar 

  • Maier AB, Westendorp RG (2009) Relation between replicative senescence of human fibroblasts and life history characteristics. Ageing Res Rev 8(3):237–243. doi:10.1016/j.arr.2009.01.004

    CAS  PubMed  Google Scholar 

  • Majora M, Wittkampf T, Schuermann B, Schneider M, Franke S, Grether-Beck S, Wilichowski E, Bernerd F, Schroeder P, Krutmann J (2009) Functional consequences of mitochondrial DNA deletions in human skin fibroblasts: increased contractile strength in collagen lattices is due to oxidative stress-induced lysyl oxidase activity. Am J Pathol 175(3):1019–1029. doi:10.2353/ajpath.2009.080832

    CAS  PubMed Central  PubMed  Google Scholar 

  • Makrantonaki E, Zouboulis CC (2007) William J. Cunliffe Scientific Awards. Characteristics and pathomechanisms of endogenously aged skin. Dermatology 214(4):352–360. doi:10.1159/000100890

    PubMed  Google Scholar 

  • Makrantonaki E, Zouboulis CC (2011) Molecular etiology of skin aging. How important is the genetic make-up? Hautarzt 62(8):582–587. doi:10.1007/s00105-011-2136-7

    CAS  PubMed  Google Scholar 

  • McKenzie IA, Biernaskie J, Toma JG, Midha R, Miller FD (2006) Skin-derived precursors generate myelinating Schwann cells for the injured and dysmyelinated nervous system. J Neurosci 26(24):6651–6660. doi:10.1523/JNEUROSCI.1007-06.2006

    CAS  PubMed  Google Scholar 

  • Medina RJ, Kataoka K, Takaishi M, Miyazaki M, Huh NH (2006) Isolation of epithelial stem cells from dermis by a three-dimensional culture system. J Cell Biochem 98(1):174–184. doi:10.1002/jcb.20757

    CAS  PubMed  Google Scholar 

  • Mera SL, Lovell CR, Jones RR, Davies JD (1987) Elastic fibres in normal and sun-damaged skin: an immunohistochemical study. Br J Dermatol 117(1):21–27

    CAS  PubMed  Google Scholar 

  • Mitchell RE (1967) Chronic solar dermatosis: a light and electron microscopic study of the dermis. J Invest Dermatol 48(3):203–220

    CAS  PubMed  Google Scholar 

  • Montagna W, Kirchner S, Carlisle K (1989) Histology of sun-damaged human skin. J Am Acad Dermatol 21(5 Pt 1):907–918

    CAS  PubMed  Google Scholar 

  • Moragas A, Castells C, Sans M (1993) Mathematical morphologic analysis of aging-related epidermal changes. Anal Quant Cytol Histol 15(2):75–82

    CAS  PubMed  Google Scholar 

  • Muffler S, Stark HJ, Amoros M, Falkowska-Hansen B, Boehnke K, Buhring HJ, Marme A, Bickenbach JR, Boukamp P (2008) A stable niche supports long-term maintenance of human epidermal stem cells in organotypic cultures. Stem Cells 26(10):2506–2515. doi:10.1634/stemcells.2007-0991

    CAS  PubMed  Google Scholar 

  • Murphy G, Docherty AJ (1992) The matrix metalloproteinases and their inhibitors. Am J Respir Cell Mol Biol 7(2):120–125

    CAS  PubMed  Google Scholar 

  • Nakajima H, Ezaki Y, Nagai T, Yoshioka R, Imokawa G (2012) Epithelial-mesenchymal interaction during UVB-induced up-regulation of neutral endopeptidase. Biochem J 443(1):297–305. doi:10.1042/BJ20111876

    CAS  PubMed  Google Scholar 

  • Naylor EC, Watson RE, Sherratt MJ (2011) Molecular aspects of skin ageing. Maturitas 69(3):249–256. doi:10.1016/j.maturitas.2011.04.011

    CAS  PubMed  Google Scholar 

  • Nishimura EK, Granter SR, Fisher DE (2005) Mechanisms of hair graying: incomplete melanocyte stem cell maintenance in the niche. Science 307(5710):720–724. doi:10.1126/science.1099593

    CAS  PubMed  Google Scholar 

  • Olovnikov AM (1973) A theory of marginotomy. The incomplete copying of template margin in enzymic synthesis of polynucleotides and biological significance of the phenomenon. J Theor Biol 41(1):181–190

    CAS  PubMed  Google Scholar 

  • Ozawa T (1995) Mechanism of somatic mitochondrial DNA mutations associated with age and diseases. Biochim Biophys Acta 1271(1):177–189

    PubMed  Google Scholar 

  • Paul RG, Bailey AJ (1996) Glycation of collagen: the basis of its central role in the late complications of ageing and diabetes. Int J Biochem Cell Biol 28(12):1297–1310

    CAS  PubMed  Google Scholar 

  • Pellegrini G, Ranno R, Stracuzzi G, Bondanza S, Guerra L, Zambruno G, Micali G, De Luca M (1999) The control of epidermal stem cells (holoclones) in the treatment of massive full-thickness burns with autologous keratinocytes cultured on fibrin. Transplantation 68(6):868–879

    CAS  PubMed  Google Scholar 

  • Rhie G, Shin MH, Seo JY, Choi WW, Cho KH, Kim KH, Park KC, Eun HC, Chung JH (2001) Aging- and photoaging-dependent changes of enzymic and nonenzymic antioxidants in the epidermis and dermis of human skin in vivo. J Invest Dermatol 117(5):1212–1217. doi:10.1046/j.0022-202x.2001.01469.x

    CAS  PubMed  Google Scholar 

  • Rijken F, Bruijnzeel PL (2009) The pathogenesis of photoaging: the role of neutrophils and neutrophil-derived enzymes. J Investig Dermatol Symp Proc 14(1):67–72. doi:10.1038/jidsymp.2009.15

    CAS  PubMed  Google Scholar 

  • Rijken F, Bruijnzeel-Koomen CA (2011) Photoaged skin: the role of neutrophils, preventive measures, and potential pharmacological targets. Clin Pharmacol Ther 89(1):120–124. doi:10.1038/clpt.2010.221

    CAS  PubMed  Google Scholar 

  • Rittie L, Kang S, Voorhees JJ, Fisher GJ (2008) Induction of collagen by estradiol: difference between sun-protected and photodamaged human skin in vivo. Arch Dermatol 144(9):1129–1140. doi:10.1001/archderm.144.9.1129

    CAS  PubMed  Google Scholar 

  • Rock K, Fischer JW (2011) Role of the extracellular matrix in extrinsic skin aging. Hautarzt 62(8):591–597. doi:10.1007/s00105-011-2133-x

    CAS  PubMed  Google Scholar 

  • Rubin H (2002) The disparity between human cell senescence in vitro and lifelong replication in vivo. Nat Biotechnol 20(7):675–681. doi:10.1038/nbt0702-675

    CAS  PubMed  Google Scholar 

  • Sams WM Jr, Smith JG Jr (1961) The histochemistry of chronically sun-damaged skin. An investigation of mucopolysaccharides and basophilia in actinically damaged skin using alcian blue, Mowry’s, and Hicks-Matthaei stains, methylation, and saponification. J Invest Dermatol 37:447–453

    CAS  PubMed  Google Scholar 

  • Sandby-Moller J, Poulsen T, Wulf HC (2003) Epidermal thickness at different body sites: relationship to age, gender, pigmentation, blood content, skin type and smoking habits. Acta Derm Venereol 83(6):410–413. doi:10.1080/00015550310015419

    PubMed  Google Scholar 

  • Sander CS, Chang H, Salzmann S, Muller CS, Ekanayake-Mudiyanselage S, Elsner P, Thiele JJ (2002) Photoaging is associated with protein oxidation in human skin in vivo. J Invest Dermatol 118(4):618–625. doi:10.1046/j.1523-1747.2002.01708.x

    CAS  PubMed  Google Scholar 

  • Sardy M (2009) Role of matrix metalloproteinases in skin ageing. Connect Tissue Res 50(2):132–138. doi:10.1080/03008200802585622

    CAS  PubMed  Google Scholar 

  • Sarin KY, Artandi SE (2007) Aging, graying and loss of melanocyte stem cells. Stem Cell Rev 3(3):212–217

    CAS  PubMed  Google Scholar 

  • Scharffetter-Kochanek K, Brenneisen P, Wenk J, Herrmann G, Ma W, Kuhr L, Meewes C, Wlaschek M (2000) Photoaging of the skin from phenotype to mechanisms. Exp Gerontol 35(3):307–316

    CAS  PubMed  Google Scholar 

  • Schneider LA, Wlaschek M, Scharffetter-Kochanek K (2003) Skin aging–clinical aspects and pathogenesis. J Dtsch Dermatol Ges 1(3):223–232; quiz 233–234

    PubMed  Google Scholar 

  • Schuler G, Steinman RM (1985) Murine epidermal Langerhans cells mature into potent immunostimulatory dendritic cells in vitro. J Exp Med 161(3):526–546

    CAS  PubMed  Google Scholar 

  • Schuster C, Vaculik C, Fiala C, Meindl S, Brandt O, Imhof M, Stingl G, Eppel W, Elbe-Burger A (2009) HLA-DR+ leukocytes acquire CD1 antigens in embryonic and fetal human skin and contain functional antigen-presenting cells. J Exp Med 206(1):169–181. doi:10.1084/jem.20081747

    CAS  PubMed Central  PubMed  Google Scholar 

  • Schwartz E, Cruickshank FA, Christensen CC, Perlish JS, Lebwohl M (1993) Collagen alterations in chronically sun-damaged human skin. Photochem Photobiol 58(6):841–844

    CAS  PubMed  Google Scholar 

  • Shi CM, Cheng TM (2004) Differentiation of dermis-derived multipotent cells into insulin-producing pancreatic cells in vitro. World J Gastroenterol 10(17):2550–2552

    PubMed  Google Scholar 

  • Shi C, Zhu Y, Su Y, Cheng T (2006) Stem cells and their applications in skin-cell therapy. Trends Biotechnol 24(1):48–52. doi:10.1016/j.tibtech.2005.11.003

    CAS  PubMed  Google Scholar 

  • Shih DT, Lee DC, Chen SC, Tsai RY, Huang CT, Tsai CC, Shen EY, Chiu WT (2005) Isolation and characterization of neurogenic mesenchymal stem cells in human scalp tissue. Stem Cells 23(7):1012–1020. doi:10.1634/stemcells.2004-0125

    CAS  PubMed  Google Scholar 

  • Shuster S, Black MM, McVitie E (1975) The influence of age and sex on skin thickness, skin collagen and density. Br J Dermatol 93(6):639–643

    CAS  PubMed  Google Scholar 

  • Sjerobabski-Masnec I, Situm M (2010) Skin aging. Acta Clin Croat 49(4):515–518

    PubMed  Google Scholar 

  • Slominski A, Paus R (1993) Melanogenesis is coupled to murine anagen: toward new concepts for the role of melanocytes and the regulation of melanogenesis in hair growth. J Invest Dermatol 101(1 Suppl):90S–97S

    CAS  PubMed  Google Scholar 

  • Sprecher E, Becker Y, Kraal G, Hall E, Harrison D, Shultz LD (1990) Effect of aging on epidermal dendritic cell populations in C57BL/6 J mice. J Invest Dermatol 94(2):247–253

    CAS  PubMed  Google Scholar 

  • Steingrimsson E, Copeland NG, Jenkins NA (2005) Melanocyte stem cell maintenance and hair graying. Cell 121(1):9–12. doi:10.1016/j.cell.2005.03.021

    CAS  PubMed  Google Scholar 

  • Stern MM, Bickenbach JR (2007) Epidermal stem cells are resistant to cellular aging. Aging Cell 6(4):439–452. doi:10.1111/j.1474-9726.2007.00318.x

    CAS  PubMed  Google Scholar 

  • Sugimoto M, Yamashita R, Ueda M (2006) Telomere length of the skin in association with chronological aging and photoaging. J Dermatol Sci 43(1):43–47. doi:10.1016/j.jdermsci.2006.02.004

    CAS  PubMed  Google Scholar 

  • Sumino H, Ichikawa S, Abe M, Endo Y, Nakajima Y, Minegishi T, Ishikawa O, Kurabayashi M (2004) Effects of aging and postmenopausal hypoestrogenism on skin elasticity and bone mineral density in Japanese women. Endocr J 51(2):159–164

    CAS  PubMed  Google Scholar 

  • Thornton MJ (2013) Estrogens and aging skin. Dermato-Endocrinology 5(2):264–270. doi:10.4161/derm.23872

    PubMed Central  PubMed  Google Scholar 

  • Tigges J, Krutmann J, Fritsche E, Haendeler J, Schaal H, Fischer JW, Kalfalah F, Reinke H, Reifenberger G, Stuhler K, Ventura N, Gundermann S, Boukamp P, Boege F (2014) The hallmarks of fibroblast ageing. Mech Ageing Dev. doi:10.1016/j.mad.2014.03.004

    PubMed  Google Scholar 

  • Toma JG, Akhavan M, Fernandes KJ, Barnabe-Heider F, Sadikot A, Kaplan DR, Miller FD (2001) Isolation of multipotent adult stem cells from the dermis of mammalian skin. Nat Cell Biol 3(9):778–784. doi:10.1038/ncb0901-778

    CAS  PubMed  Google Scholar 

  • Toma JG, McKenzie IA, Bagli D, Miller FD (2005) Isolation and characterization of multipotent skin-derived precursors from human skin. Stem Cells 23(6):727–737. doi:10.1634/stemcells.2004-0134

    CAS  PubMed  Google Scholar 

  • Trounce I, Byrne E, Marzuki S (1989) Decline in skeletal muscle mitochondrial respiratory chain function: possible factor in ageing. Lancet 1(8639):637–639

    CAS  PubMed  Google Scholar 

  • Tzellos TG, Klagas I, Vahtsevanos K, Triaridis S, Printza A, Kyrgidis A, Karakiulakis G, Zouboulis CC, Papakonstantinou E (2009) Extrinsic ageing in the human skin is associated with alterations in the expression of hyaluronic acid and its metabolizing enzymes. Exp Dermatol 18(12):1028–1035. doi:10.1111/j.1600-0625.2009.00889.x

    CAS  PubMed  Google Scholar 

  • Uitto J (1986) Connective tissue biochemistry of the aging dermis. Age-related alterations in collagen and elastin. Dermatol Clin 4(3):433–446

    CAS  PubMed  Google Scholar 

  • Uitto J (1997) Understanding premature skin aging. N Engl J Med 337(20):1463–1465. doi:10.1056/NEJM199711133372011

    CAS  PubMed  Google Scholar 

  • Uitto J, Paul JL, Brockley K, Pearce RH, Clark JG (1983) Elastic fibers in human skin: quantitation of elastic fibers by computerized digital image analyses and determination of elastin by radioimmunoassay of desmosine. Lab Invest 49(4):499–505

    CAS  PubMed  Google Scholar 

  • Velling T, Risteli J, Wennerberg K, Mosher DF, Johansson S (2002) Polymerization of type I and III collagens is dependent on fibronectin and enhanced by integrins alpha 11beta 1 and alpha 2beta 1. J Biol Chem 277(40):37377–37381. doi:10.1074/jbc.M206286200

    CAS  PubMed  Google Scholar 

  • 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(3):145–154. doi:10.1111/j.0909-752X.2006.00146.x

    PubMed  Google Scholar 

  • Warren R, Gartstein V, Kligman AM, Montagna W, Allendorf RA, Ridder GM (1991) Age, sunlight, and facial skin: a histologic and quantitative study. J Am Acad Dermatol 25(5 Pt 1):751–760

    CAS  PubMed  Google Scholar 

  • Watson JD (1972) Origin of concatemeric T7 DNA. Nat New Biol 239(94):197–201

    CAS  PubMed  Google Scholar 

  • Weinberg RA (2006) The biology of cancer. Science, Garland

    Google Scholar 

  • West MD (1994) The cellular and molecular biology of skin aging. Arch Dermatol 130(1):87–95

    CAS  PubMed  Google Scholar 

  • Whitton JT, Everall JD (1973) The thickness of the epidermis. Br J Dermatol 89(5):467–476

    CAS  PubMed  Google Scholar 

  • Winter MC, Bickenbach JR (2009) Aging epidermis is maintained by changes in transit-amplifying cell kinetics, not stem cell kinetics. J Invest Dermatol 129(11):2541–2543. doi:10.1038/jid.2009.236

    CAS  PubMed  Google Scholar 

  • Wu S, Li H, Zhang X, Li Z (2012) Optical features for chronological aging and photoaging skin by optical coherence tomography. Lasers Med Sci. doi:10.1007/s10103-012-1069-4

    Google Scholar 

  • Xu YP, Qi RQ, Chen W, Shi Y, Cui ZZ, Gao XH, Chen HD, Zhou L, Mi QS (2012) Aging affects epidermal Langerhans cell development and function and alters their miRNA gene expression profile. Aging (Albany N Y) 4(11):742–754

    CAS  Google Scholar 

  • Yaar M, Gilchrest BA (2001) Ageing and photoageing of keratinocytes and melanocytes. Clin Exp Dermatol 26(7):583–591

    CAS  PubMed  Google Scholar 

  • Yaar M, Gilchrest BA (2007) Photoageing: mechanism, prevention and therapy. Br J Dermatol 157(5):874–887. doi:10.1111/j.1365-2133.2007.08108.x

    CAS  PubMed  Google Scholar 

  • Yamamoto Y, Gaynor RB (2001) Therapeutic potential of inhibition of the NF-kappaB pathway in the treatment of inflammation and cancer. J Clin Invest 107(2):135–142. doi:10.1172/JCI11914

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yamauchi M, Woodley DT, Mechanic GL (1988) Aging and cross-linking of skin collagen. Biochem Biophys Res Commun 152(2):898–903

    CAS  PubMed  Google Scholar 

  • Yan W, Zhao Z, Zhang L, Wang D, Yan L, Yin N, Wu D, Zhang F (2011) Identification of estrogen-associated intrinsic aging genes in Chinese Han female skin by cDNA microarray technology. Biomed Environ Sci 24(4):364–373. doi:10.3967/0895-3988.2011.04.007

    CAS  PubMed  Google Scholar 

  • Yen TC, Chen YS, King KL, Yeh SH, Wei YH (1989) Liver mitochondrial respiratory functions decline with age. Biochem Biophys Res Commun 165(3):944–1003

    CAS  PubMed  Google Scholar 

  • Zouboulis CC (2003) Intrinsic skin aging. A critical appraisal of the role of hormones. Hautarzt 54(9):825–832. doi:10.1007/s00105-003-0581-7

    PubMed  Google Scholar 

  • Zouboulis CC, Makrantonaki E (2011) Clinical aspects and molecular diagnostics of skin aging. Clin Dermatol 29(1):3–14. doi:10.1016/j.clindermatol.2010.07.001

    PubMed  Google Scholar 

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Acknowledgment

The authors are grateful to Monika Bock for her help in editing the manuscript. This work was supported by grants from the German Research Foundation (SFB873) and the BMBF GerontoSys Stromal Aging (031.5576B) and UVA Kompetenzverbund (02NUK003A).

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  1. Genetics of Skin Carcinogenesis, German Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg, 69120, Germany

    Sabrina Gundermann, Hans-Jürgen Stark & Petra Boukamp

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  1. Sabrina Gundermann
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  2. Hans-Jürgen Stark
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  3. Petra Boukamp
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Correspondence to Petra Boukamp .

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  1. Dermatology and Allergic Diseases, Ulm University, Ulm, Germany

    Hartmut Geiger

  2. Department of Biology, University of Rochester, Rochester, New York, USA

    Heinrich Jasper

  3. Dermatology and Allergic Diseases, Ulm University, Ulm, Germany

    Maria Carolina Florian

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Gundermann, S., Stark, HJ., Boukamp, P. (2015). Aging of Stem Cells in Skin: What Is Driving the Aging Process?. In: Geiger, H., Jasper, H., Florian, M. (eds) Stem Cell Aging: Mechanisms, Consequences, Rejuvenation. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1232-8_8

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