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Factors of skin ageing share common mechanisms

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Abstract

Ageing has been defined as the accumulation of molecular modificationswhich manifest as macroscopic clinical changes. Human skin, unique amongmammalians insofar as it is deprived of fur, is particularly sensitiveto environmental stress. Major environmental factors have beenrecognized to induce modifications of the morphological and biophysicalproperties of the skin. Metabolites from ingested or inhaled substancesdo affect skin, which is also sensitive to endogenous hormone levels.Factors as diverse as ultraviolet radiation, atmospheric pollution,wounds, infections, traumatisms, anoxya, cigarette smoke, and hormonalstatus have a role in increasing the rate of accumulation of molecularmodifications and have thus been termed 'factors of ageing'. All thesefactors share as a common feature, the capability to directly orindirectly induce one of the steps of the micro-inflammatory cycle,which includes the expression of ICAM-1 in endothelial cells. Thistriggers a process leading to the accumulation of damages in the skinresulting in skin ageing since ICAM-1 expression provokes recruitmentand diapedesis of circulating immune cells, which digest theextracellular matrix (ECM) by secreting collagenases, myeloperoxidasesand reactive oxygen species. The activation of these lytic processesprovokes random damage to resident cells, which in turn secreteprostaglandines and leukotrienes. These signaling molecules induce thedegranulation of resident mast cells which release the autacoidhistamine and the cytokine TNF-α thus activating endothelial cellslining adjacent capillaries which release P-selectin and synthesizeICAM-1. This closes a self-maintained micro-inflammatory cycle, whichresults in the accumulation of ECM damage, i.e. skin aging. In thispaper we review the evidence that two factors able to inducemacroscopical and molecular modifications in the skin, protein glycationand stretch, activate the micro-inflammatory cycle. We further presentevidence that three additional factors, two external factors(electromagnetic fields and psychological stressors) and one internalfactor (neuropeptides) also activate the micro-inflammatory cycles andmay therefore be considered as factors of skin ageing.

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References

  • Ader R (1980) Psychosomatic and psychoimmunologic research. Psychosomatic Med 42: 307-321

    Google Scholar 

  • Ansel JC, Kaynard AH, Armstrong CA, Olerud J, Bunnett N and Payan D (1996) Skin-nervous system interactions. J Invest Dermatol 106: 198-204

    PubMed  Google Scholar 

  • Alstergren P, Ernberg M, Kopp S, Lundeberg T and Theodorsson E (1999) TMJ pain in relation to circulating neuropeptide Y, serotonin, and interleukin-1 beta in rheumatoid arthritis. J Orofac Pain 13: 49-55

    PubMed  Google Scholar 

  • Airaksinen KEJ, Salmela PI, Linnaluoto MK, Ikaheimo MJ, Ahola K and Ryhanen LJ (1993) Diminished arterial elasticity in diabetes: association with fluorescent advanced glycosylation end products in collagen Cardiovasc Res 27: 942-945

    PubMed  Google Scholar 

  • Anfinogenov VA, Vasil'ev AV, Mymirina IA and Terskikh VV (1991) The interaction of epidermal keratinocytes and fibroblasts during the formation of a live skin equivalent. Tsitologija 34: 60-65

    Google Scholar 

  • Bjorklund H, Dalsgaard CJ, Jonsson CE and Hermansson A (1986) Sensory and autonomic innervation on non-hairy and hairy human skin. Cell Tissue Res 243: 51-62

    PubMed  Google Scholar 

  • Brownlee M, Vlassara H, Kooney T, Ulrich P and Cerami A (1986) Aminoguanidine prevents diabetes-induced arterial wall protein cross-linking. Science 232: 1629-1632

    PubMed  Google Scholar 

  • Charonis AS, Reger LA, Dege JE, Kouzi-Koliakos K, Furcht LT, Wohlhueter RM and Tsilibary RC (1990) Laminin alterations after in vitro non-enzymatic glucosylation. Diabetes 39: 807-814

    PubMed  Google Scholar 

  • Conrad CD and McEwen BS (2000) Acute stress increases neuropeptide Y mRNA within the arcuate nucleus and hilus of the dentate gyrus. Brain Res Mol Brain Res 79: 102-109

    PubMed  Google Scholar 

  • Cossarizza A, Angioni S, Petraglia F, Genazzani AR, Monti D, Capri M, Bersani F, Cadossi R and Franceschi C (1993) Exposure to low-frequency pulsed electromagnetic fields increases interleukin-1 and interleukin-6 production by human peripheral blood mononuclear cells. Exp Cell Res 204: 385-387

    PubMed  Google Scholar 

  • Denda M, Tsuchiya T, Elias PM and Feingold KR (2000) Stress alters cutaneous permeability barrier homeostasis Am J Physiol Regul Integr Comp Physiol 278: 367-372

    Google Scholar 

  • Donnellan M, McKenzie DR and French PW (1997) Effects of exposure to electromagnetic radiation at 835 MHz on growth, morphology and secretory characteristics of a mast cell analogue, RBL-2H3 Cell Biol Int 21: 427-439

    Google Scholar 

  • Dunn JA, McCance DR, Thorpe SR, Lyons TJ and Baynes JW (1991) Age-dependent accumulation of N(ɛ)-(carboxymethyl) lysine and N(ɛ)-(carboxymethyl)hydroxylysine in human skin collagen. Biochemistry 30: 1205-1210

    PubMed  Google Scholar 

  • Dyer DG, Blackledge JA, Katz BM, Hull CJ, Adkisson HD, Thorpe SR, Lyons TJ and Baynes JW (1991) The Maillard reaction in vivo. Z Ernahrungswiss 30: 29-45

    PubMed  Google Scholar 

  • Dyer DG, Dunn JA, Thorpe SR, Bailie KE, Lyons TJ, McCance DR and Baynes JW (1993) Accumulation of Maillard reaction products in skin collagen in diabetes and ageing. J Clin Invest 91: 2463-2469

    PubMed  Google Scholar 

  • Eastwood M, McGrouther DA and Brown RA (1994) A culture force monitor for measurement of contraction forces generated in human dermal fibroblast cultures: evidence for cell-matrix signaling. Biochem Biophys Acta 120: 186-192

    Google Scholar 

  • Eastwood M, McGrouther DA and Brown RA (1998) Fibroblast response to mechanical forces. Proc Inst Mech Eng [H] 212: 85-92

    Google Scholar 

  • Farber EM, Rein G and Lanigan SW (1991) Stress and psoriasis: psychoneuroimmunologic mechanisms. Internat J Dermatol 30: 8-12

    Google Scholar 

  • Fluck J, Querfeld C, Cremer A, Niland S, Krieg T and Sollberg S (1998) Normal human primary fibroblasts undergo apoptosis in three-dimensional contractile collagen gels. J Invest Dermatol 110: 153-157

    PubMed  Google Scholar 

  • Fischer EG, Stingl A and Kirkpatrick CJ (1990) Opioid influence on the adherence of granulocytes to human umbilical vein endothelial cells in vitro. Cell Biol Int Rep 14: 797-804

    PubMed  Google Scholar 

  • Forman JC (1987) Substance P and calcitonin gene-related peptide: effects on mast cells and in human skin. Int Archs Allergy Appl Immunol 82: 366-373

    Google Scholar 

  • Fray TR, Molloy JE, Armitage MP and Sparrow JC (1998) Quantifi-cation of a single human dermal fibroblast contraction Tissue Eng 4: 281-291

    PubMed  Google Scholar 

  • Gangi S and Johansson O (2000) A theoretical model based upon mast cell and histamine to explain the recently proclaimed sensitivity to electric and/or magnetic fields in humans. Med Hypotheses 54: 663-671

    PubMed  Google Scholar 

  • Garaj-Vrhovac V, Horvat D and Koren Z (1991) The relationship between colony-forming ability, chromosome aberrations and incidence of micronuclei in V79 Chinese hamster cells exposed to microwave radiation. Mutat Res 263: 143-149

    PubMed  Google Scholar 

  • Garg A, Chren MM, Sands LP, Matsui MS, Marenus KD, Feingold KR and Elias PM 2001) Psychological stress perturbs epidermal permeability barrier homeostasis: implications for the pathogenesis of stress-associated skin disorders. Arch Dermatol 137: 53-59

    PubMed  Google Scholar 

  • Gerra G, Zaimovic A, Zambelli U, Timpano M, Reali N, Bernasconi S and Brambilla F (2000) Neuroendocrine responses to psychological stress in adolescents with anxiety disorder. Neuropsychobiology 42: 82-92

    PubMed  Google Scholar 

  • Giacomoni PU (1992) Ageing and cellular defense mechanisms. In: Franceschi C, Crepaldi G, Cristofalo VJ and Vijg J (eds) Ageing and Cellular Defense Mechanisms, Vol 663, pp 1-3. Ann NY Acad Sci

  • Giacomoni PU (1995) Radiazione Ultravioletta, Invecchiamento e Blebs. Giornale di Gerontologia 43: 209-210

    Google Scholar 

  • Giacomoni PU and D'Alessio, P (1996a) Skin ageing: the relevance of anti-oxidants. In: Rattan SIS and Toussaints O (eds) Molecular Gerontology: Research Status and Strategies, pp 177-192. Plenum Press, New York

    Google Scholar 

  • Giacomoni PU and D'Alessio P (1996b) Open questions in photobiology IV: photoageing of the skin. J Photochem Photobiol B: Biol 33: 267-272

    Google Scholar 

  • Giacomoni PU, Declercq L, Hellemans L and Maes D (2000) Ageing of human skin: review of a mechanistic model and first experimental data. IUBMB Life 49: 259-263

    PubMed  Google Scholar 

  • Guidi L, Tricerri A, Vangeli M, Frasca D, Riccardo Errani A, Di Giovanni A, Antico L, Menini E, Sciamanna V, Magnavita N, Doria G and Bartoloni C (1999) Neuropeptide Y plasma levels and immunological changes during academic stress. Neuropsychobio 40: 188-195

    Google Scholar 

  • Hufeland CW (1798) L'Arte di prolungare la vita umana [Italian translation by Luigi Careno]. Vol II, pp 174ff. Eredi di Pietro Galeazzi, Pavia

    Google Scholar 

  • Johansson O, Hilliges M, Bjoernhagen V and Hall K (1994) Skin changes in patients claiming to suffer from 'screen dermatitis': a two-case open-field provocation study. Exp Dermatol 3: 234-238

    PubMed  Google Scholar 

  • Johansson O, Hilliges M and Han SW (1996) A screening of skin changes, with special emphasis on neurochemical marker antibody evaluation, in patients claiming to suffer from 'screen dermatitis' as compared to normal healthy controls. Exp Dermatol 5: 279-285

    PubMed  Google Scholar 

  • Johnston JA, Taub DD, Lloyd AR, Conlon K, Oppenheim JJ and Kevlin DJ (1994) Human T lymphocyte chemotaxis and adhesion induced by vasoactive intestinal peptide. J Immunol 153: 1762-1768

    PubMed  Google Scholar 

  • Kavelaars A, Jeurissen F and Heijnrn CJ (1994) Substance P receptors and signal transduction in leukocytes. Immunomethods 5: 41-48

    PubMed  Google Scholar 

  • Kent MJC, Light ND and Bailey AJ (1985) Evidence for glucosemediated covalent cross-linking of collagen after glycosylation in vitro. Biochem J 225: 745-752

    PubMed  Google Scholar 

  • Koks S, Mannisto PT, Bourin M, Shlik J, Vasar V and Vasar E (2000) Cholecystokinin-induced anxiety in rats: relevance of pre-experimental stress and seasonal variations. J Psychiatry Neurosci 25: 33-42

    PubMed  Google Scholar 

  • Kudielka BM, Schmidt-Reinwald AK, Hellhammer DH and Kirschbaum C (1999) Psychological and endocrine responses to psychosocial stress and dexamethasone/corticotropin-releasing hormone in healthy postmenopausal women and young controls. Neuroendocrinology 70: 422-430

    PubMed  Google Scholar 

  • Kunt T, Forst T, Harzer O, Buchert G, Pfutzner A, Lobig M, Zschabitz A, Stofft E, Engelbach M and Beyer J (1998) The influence of advanced glycation endproducts (AGE) on the expression of human endothelial adhesion molecules. Exp Clin Endocrinol Diabetes 106: 183-188

    PubMed  Google Scholar 

  • Lamb RG, Harper CC, McKinney JS, Rzigalinski BA and Ellis EF (1997) Alterations in phosphatidylcholine metabolism of stretchinjured cultured rat astrocytes. J Neurochem 68: 1904-1910

    PubMed  Google Scholar 

  • Maes A, Verschaeve L, Arroyo A, De Wagter C and Vercruyssen L (1993) In vitro cytogenetic effects of 2450 MHz waves on human periferal blood lymphocytes. Bioelectromagnetics 1: 495-501

    Google Scholar 

  • Matis WL, Lavker RM and Murphy GF (1990) Substance P induces the expression of an endothelial-leukocyte adhesion molecule by microvascular endothelium. J Invest Dermatol 94: 492-498

    PubMed  Google Scholar 

  • McKinney JS, Willoughby KA, Liang S and Ellis EF (1996) Stretchinduced injury of cultured neural, glial and endothelial cells. Effect of polyethylene glycol-conjugated superoxide dismutase. Stroke 27: 934-940

    PubMed  Google Scholar 

  • Melling M, Pfeiler W, Karimian-Teherani D, Schnallinger M, Sobal G, Zangerle C and Menzel EJ (2000) Differential scanning calorimetry, biochemical and biomechanical analysis of human skin from individual with diabetes mellitus Anat Rec 259: 327-333

    PubMed  Google Scholar 

  • Mizutari K, Ono T, Ikeda K, Kayashima K and Horiuchi S (1997) Photo-enhanced modification of human skin elastin in actinic elastosis by N (ɛ)-carboxymethyl)lysine, one of the glycoxidation products of the Maillard reaction. J Invest Dermatol 108: 797-802

    PubMed  Google Scholar 

  • Monnier V and Cerami A (1983) Detection of nonenzymatic browning products in the human lens Biochem Biophys Acta 760: 97-103

    PubMed  Google Scholar 

  • Monnier VM, Sell DR, Abdul-Karim FW and Emancipator SN (1988) Collagen browning and cross linking are increased in chronic experimental hyperglycemia: relevance to diabetes and ageing. Diabetes 37: 867-872

    PubMed  Google Scholar 

  • Morandi MA, Del Rio JA, Caren RP and Caren LD (1994) Effects of short term exposure to 60 Hz electromagnetic fields on interleukin 1 and interleukin 6 production by peritoneal exudate cells. Life Sci 54: 731-738

    PubMed  Google Scholar 

  • Morgan CA, Wang S, Southwick SM, Rasmusson A, Hazlett G, Hauger RI and Charney DS (2000) Plasma neuropeptide-Y concentrations in humans exposed to military survival training. Biol Psychiatry 47: 902-909

    PubMed  Google Scholar 

  • Mousa SA, Machelska H, Schafer M and Stein C (2000) Coexpression of beta-endorphin with adhesion molecules in a model of inflammatory pain. J Neuroimmunol 108: 160-170

    PubMed  Google Scholar 

  • Nakagawa N, Iwamoto I and Yoshida S (1993) Effect of substance P on the expression of an adhesion molecule ICAM-1 in human vascular endothelial cells. Regul Pept 46: 223-224

    PubMed  Google Scholar 

  • Odetti PR, Borgoglio A and Rolandi R (1992) Age-related increase of collagen fluorescence in human sub-cutaneous tissue. Metabolism 41: 655-658

    PubMed  Google Scholar 

  • Oehme P, Hecht K, Faulhaber HD, Nieber K, Roske I and Rathsack R (1987) Relationship of substance P to catecholamines, stress and hypertension. J Cardiovasc Pharmacol Suppl 12: S109-S111.

    Google Scholar 

  • Ortega E, Forner MA and Barriga C (1996) Effect of beta-endorphin on adherence, chemotaxic and phagocytosis of Candida Albicans by peritoneal macrophages. Comp Immunol Microbiol Infect Dis 19: 267-274

    PubMed  Google Scholar 

  • Payan D, Brewster D and Goetzl E (1993) Specific stimulation of human T lymphocytes by substance P. J Immunol 131: 1613-1615

    Google Scholar 

  • Quinlan KL, Song IS, Bunnett NW, Letran E, Steinhoff M, Harten B, Olerud JE, Armstrong CA, Wright Caughman S and Ansel JC (1998) Neuropeptide regulation of human dermal microvascular endothelial cell ICAM-1 expression and function. Am J Physiol 275: C1580-C1590

    PubMed  Google Scholar 

  • Quinlan KL, Naik SM, Cannon G, Armstrong CA, Bunnett NW, Ansel JC and Caughman SW (1999) Substance P activates coincident NF-AT-and NF-kappa B-dependent adhesion molecule gene expression in microvascular endothelial cells 229 through intracellular calcium mobilization. J Immunol 163: 5656-5665

    PubMed  Google Scholar 

  • Raud J, Lundeberg T, Brodda-Jansen G et al. (1991) Potent antiinflammatory action of calcitonin-gene-related peptide. Biochem Biophys Res Comm 180: 1429-1435

    PubMed  Google Scholar 

  • Ren J, Goa J, Ojeas H, Lightfoot SA, Kida M, Brewer K and Harty RF (2000) Involvement of capsaicin-sensitive sensory neurons in stress-induced gastroduodenal mucosal injury in rats. Dig Dis Sci 45: 830-836

    PubMed  Google Scholar 

  • Robert L and Labat-Robert J (2000) Ageing of connective tissues: from genetic to epigenetic mechanisms. Biogenrontology 1: 123-131

    Google Scholar 

  • Rupniak NM, Carlson EC, Harrison T, Oates B, Seward E, Owen S, deFelipe C, Hunt S and Wheeldon A (2000) Pharmacological blockade or genetic deletion of substance P (NK(1)) receptors attenuates neonatal vocalisation in guinea-pigs and mice. Neuropharmacology 39: 1413-1421

    PubMed  Google Scholar 

  • Rzigalinski BA, Weber JT, Willoughby KA and Ellis EF (1998) Intracellular free calcium dynamics in stretch-injured astrocytes. J Neurochem 70: 2377-2385

    PubMed  Google Scholar 

  • Singh LK, Pang X, Alexacos N, Letourneau R and Theoharides TC (1999) Acute immobilization stress triggers skin mast cell degranulation via corticotropin releasing hormone, neurotensin, and substance P: a link to neurogenic skin disorders. Brain Behav Immunol 13: 225-239

    Google Scholar 

  • Slominski A, Wortsman J, Luger T, Paus R and Solomon S (2000) Corticotropin releasing hormone and proopiomelanocortin involvement in the cutaneous response to stress. Physiol Rev 80: 979-1020

    PubMed  Google Scholar 

  • Smith CH, Barker JN, Morris RW, MacDonald DM and Lee TH (1993) Neuropeptides induce rapid expression of endothelial cell adhesion molecules and elicit granulocytic infiltration in human skin. J Immunol 151: 3274-3282

    PubMed  Google Scholar 

  • Steplewski Z and Vogel HW 1986) Total leukocytes, T cell subpopulation and natural killer (NK) activity in rats exposed to restraint stress. Life Sci 38: 2419-2425

    PubMed  Google Scholar 

  • Sung CP, Arleth AJ and Feuerstein GZ (1991) Neuropeptide Y upregulates the adhesiveness of human endothelial cells for leukocytes. Circ Res 68: 314-318

    PubMed  Google Scholar 

  • Sung CP, Arleth AJ, Aiyar N, Bhatnagar PK, Lysko PG and Feuerstein G (1992) CGRP stimulates the adhesion of leukocytes to vascular endothelial cells. Peptides 13: 429-435

    PubMed  Google Scholar 

  • Tanaka S, Avigad G, Brodsky B and Eikenberry EF (1988) Glycation induces expansion of the molecular packing of collagen. J Mol Biol 203: 495-505

    PubMed  Google Scholar 

  • Teofoli P, Frezzolini A, Puddu P, De Pita O, Mauviel A and Lotti T (1999) The role of proopiomelanocortin-derived peptides in skin fibroblasts and mast cell functions. Ann NY Acad Sci 885: 268-276

    PubMed  Google Scholar 

  • Tominaga K, Honda K, Akahoshi A, Makino Y, Kawarabayashi T, Takano Y and Kamiya H (1999) Substance P causes adhesion of neutrophils to endothelial cells via protein kinase C. Biol Pharm Bull 22: 1242-1245

    PubMed  Google Scholar 

  • Tsilibary EC, Charonis AS, Reger LA, Wohlhueter RM and Furcht LT (1988) The effect of non enzymatic glycosylation on the binding of the non collagenous NC1 domain to collagen IV. J Biol Chem 263: 4302-4308

    PubMed  Google Scholar 

  • Verzijl N, DeGroot J, Thorpe SR, Bank RA, Shaw JN, Lyons TJ, Bijlsma JW, Lafeber FP, Baynes JW and Te Koppele JM (2000) Effect of collagen turnover on the accumulation of advanced glycation endproducts. J Biol Chem 275: 39027-39031

    PubMed  Google Scholar 

  • Vishwanath R and Mukherjee R (1996) Substance P promotes lymphocyte-endothelial cell adhesion preferentially via LFA-1/ICAM-1 interactions. J Neuroimmunol 71: 163-171

    PubMed  Google Scholar 

  • Vishwanath V, Frank KE, Elmets CA, Dauchot PJ and Monnier VM (1986) Glycation of skin collagen in type I diabetes mellitus. Correlation with long-term complications Diabetes 35: 916-921

    Google Scholar 

  • Vlassara H, Valinsky J, Brownlee M, Cerami C, Nishimoto S and Cerami A (1987) Advanced glycosylation end products on erythrocyte cell surface induce receptor-mediated phagocytosis by macrophages. A model for turnover of ageing cells. J Exp Med 166: 539-549

    PubMed  Google Scholar 

  • Vlassara H, Fuh H, Donnelly T and Cybulsky M (1995) Advanced glycation endproducts promote adhesion molecule (VCAM-1, ICAM-1) expression and atheroma formation in normal rabbits Mol Med 1: 447-456

    Google Scholar 

  • Wallengren J (1997) Vasoactive peptides in the skin. J Investig Dermatol Symp Proc 2: 49-55

    PubMed  Google Scholar 

  • Williams G, Cardoso H, Ball JA, Mulderry PK, Cooke E and Bloom SR (1988) Potent and comparable vasodilator action of A-and Bcalcitonin gene related peptides on the superficial subcutaneous vasculature of man. Clin Sci 75: 309-313

    PubMed  Google Scholar 

  • Wintzen M, Zanello SB, Holick MF, Wiegant VM, Burbach JP and Vermeer BJ (2000) Condition-dependent presence of betalipotropin-like peptide in human keratinocytes. Peptides 21: 691-697

    PubMed  Google Scholar 

  • Xu IS, Luo L, Ji, RR, Hokfelt T, Xu XJ and Wiesenfeld-Hallin Z (1998) The effect of intrathecal neuropeptide Y on the flexor reflex in rats after carrageenan-induced inflammation. Neuropeptides 32: 447-452

    PubMed  Google Scholar 

  • Zanello SB, Jackson DM and Holick MF (1999) An immunocytochemical approach to the study of beta-endorphin production in human keratinocytes using confocal microscopy. Ann NY Acad Sci 885: 85-99

    PubMed  Google Scholar 

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  1. Clinique Laboratories, 125 Pinelawn Road, Melville, NY, 11747, USA

    Paolo U. Giacomoni

  2. Estee Lauder Research Park, 125 Pinelawn Road, Melville, NY, 11747, USA

    Glen Rein

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Giacomoni, P.U., Rein, G. Factors of skin ageing share common mechanisms. Biogerontology 2, 219–229 (2001). https://doi.org/10.1023/A:1013222629919

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