Abstract
Melanocytes are continuously lost from the aging hair follicle resulting in the obvious graying (canities) that visibly marks our steady decline. Many roads appear to lead to this Rome either involved in the regular aging process, or causing premature Canities. Among them, oxidative stress and an altered peri- and intrafollicular neuroendocrine milleu appear to be key mechanisms enabling or forcing melanocytes to respond to stressors ranging from exogenous oxidative stress via inflammatory stress to psychoemotional stress in a highly selective and sensitive fashion. However, growth of aging hair follicles – at least in the beginning of the process – is not affected by graying. The hair follicle melanocyte therefore appears to be a kind of sentinel indicating ongoing aging, and the presence of stressors leads to a premature decline of the hair follicle pigmentary system on the one hand, but protection from oncogenic DNA damage on the other hand.
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References
Abdel-Malek Z, Swope V, Smalara D, Babcock G, Dawes S, Nordlund J (1994) Analysis of the UV-induced melanogenesis and growth arrest of human melanocytes. Pigment Cell Res7: 326–332
Akar A, Arca E, Erbil H, Akay C, Sayal A, Gur AR (2002) Antioxidant enzymes and lipid peroxidation in the scalp of patients with alopecia areata. J Dermatol Sci 29:85–90
Arck PC, Merali FS, Manuel J, Chaouat G, Clark DA (1995) Stress-triggered abortion: inhibition of protective suppression and promotion of tumor necrosis factor-alpha (TNF-alpha) release as a mechanism triggering resorptions in mice. Am J Reprod Immunol 33:74–80
Arck PC, Handjiski B, Hagen E, Joachim R, Klapp BF, Paus R (2001) Indications for a “brain-hair follicle axis (BHA)”: inhibition of keratinocyte proliferation and up-regulation of keratinocyte apoptosis in telogen hair follicles by stress and substance P. Faseb J 15:2536–2538
Arck PC, Overall R, Spatz K, Liezman C, Handjiski B, Klapp BF et al (2006) 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 20:1567–1569
Atoyan RY, Sharov AA, Eller MS, Sargsyan A, Botchkarev VA, Gilchrest BA (2007) Oligonucleotide treatment increases eumelanogenesis, hair pigmentation and melanocortin-1 receptor expression in the hair follicle. Exp Dermatol 16: 671–677
Berking C, Takemoto R, Satyamoorthy K, Shirakawa T, Eskandarpour M, Hansson J et al (2004) Induction of melanoma phenotypes in human skin by growth factors and ultraviolet B. Cancer Res 64:807–811
Bittinger F, Gonzalez-Garcia JL, Klein CL, Brochhausen C, Offner F, Kirkpatrick CJ (1998) Production of superoxide by human malignant melanoma cells. Melanoma Res 8: 381–387
Bohr VA, Anson RM (1995) DNA damage, mutation and fine structure DNA repair in aging. Mutation Res 338: 25–34
Bowers RR, Lujan J, Biboso A, Kridel S, Varkey C (1994) Premature avian melanocyte death due to low antioxidant levels of protection: fowl model for vitiligo. Pigment Cell Res 7:409–418
Buac K, Pavan WJ (2007) Stem cells of the melanocyte lineage. Cancer Biomark 3:203–209
Bull HA, Leslie TA, Chopra S, Dowd PM (1998) Expression of nerve growth factor receptors in cutaneous inflammation. Br J Dermatol 139:776–783
Burchill SA, Thody AJ (1986) Melanocyte-stimulating hormone and the regulation of tyrosinase activity in hair follicular melanocytes of the mouse. J Endocrinol 111:225–232
Burd A, Zhu N, Poon VK (2005) A study of Q-switched Nd:YAG laser irradiation and paracrine function in human skin cells. Photodermatol Photoimmunol Photomed 21: 131–137
Cernak I, Savic V, Kotur J, Prokic V, Kuljic B, Grbovic D et al (2000) Alterations in magnesium and oxidative status during chronic emotional stress. Magnes Res 13:29–36
Chowdrey HS, Larsen PJ, Harbuz MS, Lightman SL, Jessop DS (1995) Endogenous substance P inhibits the expression of corticotropin-releasing hormone during a chronic inflammatory stress. Life Sci 57:2021–2029
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
Costin GE, Hearing VJ (2007) Human skin pigmentation: melanocytes modulate skin color in response to stress. Faseb J 21:976–994
Ditre C, Wu J, Baumann LS, Rigel D (2008) Innovations in natural antioxidants and their role in dermatology. Cutis 82:2–16
Drake WT, Issekutz AC (1993) Transforming growth factor-beta 1 enhances polymorphonuclear leucocyte accumulation in dermal inflammation and transendothelial migration by a priming action. Immunology 78:197–204
Eller MS, Puri N, Hadshiew IM, Venna SS, Gilchrest BA (2002) Induction of apoptosis by telomere 3′ overhang-specific DNA. Exp Cell Res 276:185–193
Emerit I, Filipe P, Freitas J, Vassy J (2004) Protective effect of superoxide dismutase against hair graying in a mouse model. Photochem Photobiol 80:579–582
Epel ES, Blackburn EH, Lin J, Dhabhar FS, Adler NE, Morrow JD et al (2004) Accelerated telomere shortening in response to life stress. Proc Natl Acad Sci U S A 101: 17312–17315
Flugel B (1971) The graying of hair as a criterion of biological age. Z Alternsforsch 23:397–400
Foitzik K, Lindner G, Müller-Röver S, Maurer M, Botchkareva N, Botchkarev V et al (2000) Control of murine hair follicle regression (catagen) by TGFbeta-1 in vivo. FASEB J 14(5):752–760
Fuchs J, Zollner TM, Kaufmann R, Podda M (2001) Redox-modulated pathways in inflammatory skin diseases. Free Radic Biol Med 30:337–353
Gilchrest BA, Eller MS (2005) The tale of the telomere: implications for prevention and treatment of skin cancers. J Investig Dermatol Symp Proc 10:124–130
Gilchrest BA, Park HY, Eller MS, Yaar M (1996) Mechanisms of ultraviolet light-induced pigmentation. Photochem Photobiol 63:1–10
Hara M, Toyoda M, Yaar M, Bhawan J, Avila EM, Penner IR et al (1996) Innervation of melanocytes in human skin. J Exp Med 184:1385–1395
Harman D (1956) Aging: a theory based on free radical and radiation chemistry. J Gerontol 11:298–300
Harman D (1972) The biologic clock: the mitochondria? J Am Geriatr Soc 20:145–147
Haycock JW, Rowe SJ, Cartledge S, Wyatt A, Ghanem G, Morandini R et al (2000) Alpha-melanocyte-stimulating hormone reduces impact of proinflammatory cytokine and peroxide-generated oxidative stress on keratinocyte and melanoma cell lines. J Biol Chem 275:15629–15636
Herrera B, Fernandez M, Alvarez AM, Roncero C, Benito M, Gil J et al (2001) Activation of caspases occurs downstream from radical oxygen species production, Bcl-xL down-regulation, and early cytochrome C release in apoptosis induced by transforming growth factor beta in rat fetal hepatocytes. Hepatology 34:548–556
Hockenbery DM, Oltvai ZN, Yin XM, Milliman CL, Korsmeyer SJ (1993) Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Cell 75:241–251
Inomata K, Aoto T, Binh NT, Okamoto N, Tanimura S, Wakayama T et al (2009) Genotoxic stress abrogates renewal of melanocyte stem cells by triggering their differentiation. Cell 137:1088–1099
Inoue K, Hosoi J, Ideta R, Ohta N, Ifuku O, Tsuchiya T (2003) Stress augmented ultraviolet-irradiation-induced pigmentation. J Invest Dermatol 121:165–171
Irie M, Asami S, Nagata S, Miyata M, Kasai H (2001) Relationships between perceived workload, stress and oxidative DNA damage. Int Arch Occup Environ Health 74: 153–157
Jessop DS, Harbuz MS, Lightman SL (2001) CRH in chronic inflammatory stress. Peptides 22:803–807
Jimenez-Cervantes C, Martinez-Esparza M, Perez C, Daum N, Solano F, Garcia-Borron JC (2001) Inhibition of melanogenesis in response to oxidative stress: transient downregulation of melanocyte differentiation markers and possible involvement of microphthalmia transcription factor. J Cell Sci 114:2335–2344
Krishnan KJ, Harbottle A, Birch-Machin MA (2004) The use of a 3895 bp mitochondrial DNA deletion as a marker for sunlight exposure in human skin. J Invest Dermatol 123: 1020–1024
Lafon C, Mathieu C, Guerrin M, Pierre O, Vidal S, Valette A (1996) Transforming growth factor beta 1-induced apoptosis in human ovarian carcinoma cells: protection by the antioxidant N-acetylcysteine and bcl-2. Cell Growth Differ 7: 1095–1104
Liu CS, Ko LY, Lim PS, Kao SH, Wei YH (2001) Biomarkers of DNA damage in patients with end-stage renal disease: mitochondrial DNA mutation in hair follicles. Nephrol Dial Transplant 16:561–565
Logan A, Weatherhead B (1981) Effects of alpha-melanocyte-stimulating hormone and [8-arginine]-vasotocin upon melanogenesis in hair follicle melanocytes in vitro. J Endocrinol 91:501–507
Lu Z, Fischer TW, Hasse S, Sugawara K, Kamenisch Y, Krengel S et al (2009) Profiling the response of human hair follicles to ultraviolet radiation. J Invest Dermatol 129: 1790–1804
Luger TA, Brzoska T, Scholzen TE, Kalden DH, Sunderkotter C, Armstrong C et al (2000) The role of alpha-MSH as a modulator of cutaneous inflammation. Ann N Y Acad Sci 917:232–238
Macpherson JW, Penner P (1967) Animal identification. I. Liquid nitrogen branding of cattle. Can J Comp Med Vet Sci 31:271–274
Martin M, Vozenin MC, Gault N, Crechet F, Pfarr CM, Lefaix JL (1997) Coactivation of AP-1 activity and TGF-beta1 gene expression in the stress response of normal skin cells to ionizing radiation. Oncogene 15:981–989
Martinez-Esparza M, Ferrer C, Castells MT, Garcia-Borron JC, Zuasti A (2001) Transforming growth factor beta1 mediates hypopigmentation of B16 mouse melanoma cells by inhibition of melanin formation and melanosome maturation. Int J Biochem Cell 33:971–983
Mattei S, Colombo MP, Melani C, Silvani A, Parmiani G, Herlyn M (1994) Expression of cytokine/growth factors and their receptors in human melanoma and melanocytes. Int J Cancer 56:853–857
Messenger AG, Bleehen SS (1984) Alopecia areata: light and electron microscopic pathology of the regrowing white hair. Br J Dermatol 110:155–162
Meyskens FL Jr, Farmer P, Fruehauf JP (2001) Redox regulation in human melanocytes and melanoma. Pigment Cell Res 14: 148–154
Michard Q, Commo S, Rocchetti J, El Houari F, Alleaume AM, Wakamatsu K et al (2008) TRP-2 expression protects HEK cells from dopamine- and hydroquinone-induced toxicity. Free Radical Biol Med 45:1002–1010
Miquel J, Economos AC, Fleming J, Johnson JE Jr (1980) Mitochondrial role in cell aging. Exp Gerontol 15:575–591
Moretti S, Pinzi C, Spallanzani A, Berti E, Chiarugi A, Mazzoli S et al (1999) Immunohistochemical evidence of cytokine networks during progression of human melanocytic lesions. Int J Cancer 84:160–168
Moriyama M, Osawa M, Mak SS, Ohtsuka T, Yamamoto N, Han H et al (2006) Notch signaling via Hes1 transcription factor maintains survival of melanoblasts and melanocyte stem cells. J Cell Biol 173(3):333–339
Mosley JG, Gibbs AC (1996) Premature gray hair and hair loss among smokers: a new opportunity for health education? Br Med J 313:1616
Nappi AJ, Vass E (1996) Hydrogen peroxide generation associated with the oxidations of the eumelanin precursors 5,6-dihydroxyindole and 5,6-dihydroxyindole-2-carboxylic acid. Melanoma Res 6:341–349
Nishimura EK, Jordan SA, Oshima H, Yoshida H, Osawa M, Moriyama M et al (2002) Dominant role of the niche in melanocyte stem-cell fate determination. Nature 416: 854–860
Nishimura EK, Granter SR, Fisher DE (2005) Mechanisms of hair graying: incomplete melanocyte stem cell maintenance in the niche. Science 307(5710):720–724
Nordlund JJ, Abdel-Malek ZA (1988) Mechanisms for post-inflammatory hyperpigmentation and hypopigmentation. Prog Clin Biol Res 256:219–236
Nordlund JJ, Boissy RE, Hering VJ, King RA, Ortonne J-P (1998) The pigmentary system. Oxford University Press, New York, p 1106
Patrick E, Juberg DR, J OD, Maibach HI (1999) Depigmentation with tert-butyl hydroquinone using black guinea pigs. Food Chem Toxicol 37:169–175
Paus R, Slominski A, Czarnetzki BM (1994) Is alopecia areata an autoimmune-response against melanogenesis-related proteins, exposed by abnormal MHC class I expression in the anagen hair bulb? Yale J Biol Med 66: 541–554
Peters EM, Tobin DJ, Botchkareva N, Maurer M, Paus R (2002) Migration of melanoblasts into the developing murine hair follicle is accompanied by transient c-Kit expression. J Histochem Cytochem 50:751–766
Peters EM, Handjiski B, Kuhlmei A, Hagen E, Bielas H, Braun A et al (2004) Neurogenic inflammation in stress-induced termination of murine hair growth is promoted by nerve growth factor. Am J Pathol 165:259–271
Peters EM, Kuhlmei A, Tobin DJ, Muller-Rover S, Klapp BF, Arck PC (2005) Stress exposure modulates peptidergic innervation and degranulates mast cells in murine skin. Brain Behav Immun 19:252–262
Peters EM, Stieglitz MG, Liezman C, Overall RW, Nakamura M, Hagen E et al (2006) p75 Neurotrophin receptor-mediated signaling promotes human hair follicle regression (Catagen). Am J Pathol 168:221–234
Peters EM, Liotiri S, Bodo E, Hagen E, Biro T, Arck PC et al (2007) Probing the effects of stress mediators on the human hair follicle: substance P holds central position. Am J Pathol 171:1872–1886
Picardo M, Grammatico P, Roccella F, Roccella M, Grandinetti M, Del Porto G et al (1996) Imbalance in the antioxidant pool in melanoma cells and normal melanocytes from patients with melanoma. J Invest Dermatol 107: 322–326
Pincelli C, Yaar M (1997) Nerve growth factor: its significance in cutaneous biology. J Investig Dermatol Symp Proc 2:31–36
Pittelkow MR, Shipley GD (1989) Serum-free culture of normal human melanocytes: growth kinetics and growth factor requirements. J Cell Physiol 140:565–576
Ribeiro A, Bronk SF, Roberts PJ, Urrutia R, Gores GJ (1999) The transforming growth factor beta(1)-inducible transcription factor TIEG1, mediates apoptosis through oxidative stress. Hepatology 30:1490–1497
Rosini P, De Chiara G, Lucibello M, Garaci E, Cozzolino F, Torcia M (2000) NGF withdrawal induces apoptosis in CESS B cell line through p38 MAPK activation and Bcl-2 phosphorylation. Biochem Biophys Res Commun 278: 753–759
Saha B, Singh SK, Mallick S, Bera R, Datta PK, Mandal M et al (2009) Sphingolipid-mediated restoration of Mitf expression and repigmentation in vivo in a mouse model of hair graying. Pigment Cell Melanoma Res 22:205–218
Schouwey K, Delmas V, Larue L, Zimber-Strobl U, Strobl LJ, Radtke F et al (2007) Notch1 and Notch2 receptors influence progressive hair graying in a dose-dependent manner. Dev Dyn 236(1):282–289
Sieber-Blum M (1998) Growth factor synergism and antagonism in early neural crest development. Biochem Cell Biol 76:1039–1050
Smit NP, van Nieuwpoort FA, Marrot L, Out C, Poorthuis B, van Pelt H et al (2008) Increased melanogenesis is a risk factor for oxidative DNA damage study on cultured melanocytes and atypical nevus cells. Photochem Photobiol 84: 550–555
Sternberg EM, Chrousos GP, Wilder RL, Gold PW (1992) The stress response and the regulation of inflammatory disease. Ann Intern Med 117:854–866
Taylor AW, Yee DG, Nishida T, Namba K (2000) Neuropeptide regulation of immunity. The immunosuppressive activity of alpha-melanocyte-stimulating hormone (alpha-MSH). Ann N Y Acad Sci 917:239–247
Thody AJ (1999) a-MSH and the regulation of melanocyte function. Ann N Y Acad Sci 885(1):217–229
Tobin DJ, Paus R (2001) Graying: gerontobiology of the hair follicle pigmentary unit. Exp gerontol 36:29–54
Tobin DJ, Slominski A, Botchkarev V, Paus R (1999) The fate of hair follicle melanocytes during the hair growth cycle. J Investig Dermatol Symp Proc 4:323–332
Toussaint O, Medrano EE, von Zglinicki T (2000) Cellular and molecular mechanisms of stress-induced premature senescence (SIPS) of human diploid fibroblasts and melanocytes. Exp gerontol 35:927–945
Van Neste D, Tobin DJ (2004) Hair cycle and hair pigmentation: dynamic interactions and changes associated with aging. Micron 35:193–200
Viswanathan K, Daugherty C, Dhabhar FS (2005) Stress as an endogenous adjuvant: augmentation of the immunization phase of cell-mediated immunity. Int Immunol 17:1059–1069
Wakamatsu K, Graham A, Cook D, Thody AJ (1997) Characterisation of ACTH peptides in human skin and their activation of the melanocortin-1 receptor. Pigment Cell Res 10: 288–297
Waster PK, Ollinger KM (2009) Redox-dependent translocation of p53 to mitochondria or nucleus in human melanocytes after uva- and uvb-induced apoptosis. J Invest Dermatol 129(7):1769–1781
Wei YH, Lu CY, Lee HC, Pang CY, Ma YS (1998) Oxidative damage and mutation to mitochondrial DNA and age-dependent decline of mitochondrial respiratory function. Ann N Y Acad Sci 854:155–170
Wood JM, Decker H, Hartmann H, Chavan B, Rokos H, Spencer JD et al (2009) Senile hair graying: H2O2-mediated oxidative stress affects human hair color by blunting methionine sulfoxide repair. Faseb J 23(7):2065–2075
Yaar M, Eller MS, DiBenedetto P, Reenstra WR, Zhai S, McQuaid T et al (1994) The trk family of receptors mediates nerve growth factor and neurotrophin-3 effects in melanocytes. J Clin Invest 94:1550–1562
Yamamura K, Kamada S, Ito S, Nakagawa K, Ichihashi M, Tsujimoto Y (1996) Accelerated disappearance of melanocytes in bcl-2-deficient mice. Cancer Res 56:3546–3550
Zhai S, Yaar M, Doyle SM, Gilchrest BA (1996) Nerve growth factor rescues pigment cells from ultraviolet-induced apoptosis by upregulating BCL-2 levels. Exp Cell Res 224:335–343
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Peters, E.M.J. (2010). Oxidative Stress Associated Melanocyte-Loss and Hair Growth Capacity in the Aging Hair Follicle: A Model for Tissue-Specific Aging. In: Trüeb, R., Tobin, D. (eds) Aging Hair. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-02636-2_10
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