[en] It is often described that it is difficult to really discriminate the cause of intrinsic skin aging. The aim of this study was to compare the profiles of expression of senescence-associated genes in biopsies of dermis from young and old human donors. TGF-beta1 was up-regulated in the dermis of old donors as well as the TGF-beta1-regulated genes. The anti-oxidant enzymes Selenium-dependent Glutathione peroxidase and Glutatione S-Transferase Theta 1 were also up-regulated in old dermis as well as Tumor Necrosis Factor Receptor Superfamily 1A. None of these genes had altered expression level in skin fibroblasts embedded in a collagen matrix and exposed to sublethal doses of UVB, suggesting their involvement in intrinsic aging. This study represents a proof-of-concept of larger whole transcriptome studies where all avenues should be used to subtract changes in gene expression due to extrinsic aging from changes potentially due to intrinsic aging.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Borlon, Celine; Facultés Universitaires Notre-Dame de la Paix - Namur - FUNDP > Dept of Biology, Faculty of Sciences > Research Unit on Cellular Biology
Weemaels, Geoffroy; Facultés Universitaires Notre-Dame de la Paix - Namur - FUNDP > Dept of Biology, Faculty of Sciences > Research Unit on Cellular Biology
Godard, Patrice; Facultés Universitaires Notre-Dame de la Paix - Namur - FUNDP > Dept of Biology, Faculty of Sciences > Research Unit on Cellular Biology
Debacq-Chainiaux, Florence; Facultés Universitaires Notre-Dame de la Paix - Namur - FUNDP > Dept of Biology, Faculty of Sciences > Research Unit on Cellular Biology
Lemaire, Pierre; Cente Hospitalier Regional de Namur > Geriatric Unit
Deroanne, Christophe ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Laboratoire des tissus conjonctifs
Toussaint, Olivier; Facultés Universitaires Notre-Dame de la Paix - Namur - FUNDP > Dept of Biology, Faculty of Sciences > Research Unit on Cellular Biology
Language :
English
Title :
Expression profiling of senescent-associated genes in human dermis from young and old donors. Proof-of-concept study.
Afaq F, Mukhtar H (2001) Effects of solar radiation on cutaneous detoxification pathways. J Photochem Photobiol B 63:61-69
Basu-Modak S, Gordon MJ, Dobson LH, Spencer JP, Rice-Evans C, Tyrrell RM (2003) Epicatechin and its methylated metabolite attenuate UVA-induced oxidative damage to human skin fibroblasts. Free Radic Biol Med 35:910-921
Baud V, Karin M (2001) Signal transduction by tumor necrosis factor and its relatives. Trends Cell Biol 11:372-377
Bevilacqua MA, Iovine B, Zambrano N, D'Ambrosio C, Scaloni A, Russo T, Cimino F (2005) Fibromodulin gene transcription is induced by ultraviolet irradiation, and its regulation is impaired in senescent human fibroblasts. J Biol Chem 280:31809-31817
Borlon C, Debacq-Chainiaux F, Hinrichs C, Scharffetter-Kochanek K, Toussaint O, Wlaschek M (2007a) The gene expression profile of psoralen plus UVA-induced premature senescence in skin fibroblasts resembles a combined DNA-damage and stress-induced cellular senescence response phenotype. Exp Gerontol 42:911-923
Borlon C, Godard P, Eskes C, Hartung T, Zuang V, Toussaint O (2007b) The usefulness of toxicogenomics for predicting acute skin irritation on in vitro reconstructed human epidermis. Toxicology 241:157-166
Borlon C, Vankoningsloo S, Godard P, Debacq-Chainiaux F, Toussaint O (2007c) Identification of p53-dependent genes potentially involved in UVB-mediated premature senescence of human skin fibroblasts using siRNA technology. Mech Ageing Dev. [Epub ahead of print]
Brenneisen P, Oh J, Wlaschek M, Wenk J, Briviba K, Hommel C, Herrmann G, Sies H, Scharffetter-Kochanek K (1996) Ultraviolet B wavelength dependence for the regulation of two major matrix-metalloproteinases and their inhibitor TIMP-1 in human dermal fibroblasts. Photochem Photobiol 64:877-885
Brenneisen P, Sies H, Scharffetter-Kochanek K (2002) Ultraviolet-B irradiation and matrix metalloproteinases: From induction via signaling to initial events. Ann NY Acad Sci 973:31-43
Brink N, Szamel M, Young AR, Wittern KP, Bergemann J (2000) Comparative quantification of IL-1beta, IL-10, IL-10r, TNF alpha and IL-7 mRNA levels in UV-irradiated human skin in vivo. Inflamm Res 49:290-296
Chainiaux F, Magalhaes JP, Eliaers F, Remacle J, Toussaint O (2002) UVB-induced premature senescence of human diploid skin fibroblasts. Int J Biochem Cell Biol 34:1331-1339
Chondrogianni N, de Simoes D, Franceschi C, Gonos ES (2004) Cloning of differentially expressed genes in skin fibroblasts from centenarians. Biogerontology 5:401-409
de Longueville F, Surry D, Meneses-Lorente G, Bertholet V, Talbot V, Evrard S, Chandelier N, Pike A, Worboys P, Rasson JP, Le Bourdelles B, Remacle J (2002) Gene expression profiling of drug metabolism and toxicology markers using a low-density DNA microarray. Biochem Pharmacol 64:137-149
de Magalhaes JP, Chainiaux F, de Longueville F, Mainfroid V, Migeot V, Marcq L, Remacle J, Salmon M, Toussaint O (2004) Gene expression and regulation in H2O2-induced premature senescence of human foreskin fibroblasts expressing or not telomerase. Exp Gerontol 39:1379-1389
Debacq-Chainiaux F, Borlon C, Pascal T, Royer V, Eliaers F, Ninane N, Carrard G, Friguet B, de Longueville F, Boffe S, Remacle J, Toussaint O (2005) Repeated exposure of human skin fibroblasts to UVB at subcytotoxic level triggers premature senescence through the TGF-beta1 signaling pathway. J Cell Sci 118:743-758
Delvoye P, Wiliquet P, Leveque JL, Nusgens BV, Lapiere CM (1991) Measurement of mechanical forces generated by skin fibroblasts embedded in a three-dimensional collagen gel. J Invest Dermatol 97:898-902
Derynck R, Zhang YE (2003) Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature 425:577-584
Dumont P, Burton M, Chen QM, Gonos ES, Frippiat C, Mazarati JB, Eliaers F, Remacle J, Toussaint O (2000) Induction of replicative senescence biomarkers by sublethal oxidative stresses in normal human fibroblast. Free Radic Biol Med 28:361-373
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 379:335-339
Frippiat C, Chen QM, Zdanov S, Magalhaes JP, Remacle J, Toussaint O (2001) Subcytotoxic H2O2 stress triggers a release of transforming growth factor-beta 1, which induces biomarkers of cellular senescence of human diploid fibroblasts. J Biol Chem 276:2531-2537
Frippiat C, Dewelle J, Remacle J, Toussaint O (2002) Signal transduction in H2O2-induced senescence-like phenotype in human diploid fibroblasts. Free Radic Biol Med 33:1334-1346
Fuchs J, Huflejt ME, Rothfuss LM, Wilson DS, Carcamo G, Packer L (1989) Impairment of enzymic and nonenzymic antioxidants in skin by UVB irradiation. J Invest Dermatol 93:769-773
Gaspari L, Pedotti P, Bonafe M, Franceschi C, Marinelli D, Mari D, Garte S, Taioli E (2003) Metabolic gene polymorphisms and p53 mutations in healthy centenarians and younger controls. Biomarkers 8:522-528
Gillet JP, de Longueville F, Remacle J (2006) DualChip microarray as a new tool in cancer research. Expert Rev Mol Diagn 6:295-306
Green LM, Reade JL, Ware CF (1984) Rapid colorimetric assay for cell viability: Application to the quantitation of cytotoxic and growth inhibitory lymphokines. J Immunol Methods 70:257-268
Grell M, Douni E, Wajant H, Lohden M, Clauss M, Maxeiner B, Georgopoulos S, Lesslauer W, Kollias G, Pfizenmaier K, Scheurich P (1995) The transmembrane form of tumor necrosis factor is the prime activating ligand of the 80 kDa tumor necrosis factor receptor. Cell 83:793-802
Kerb R, Brockmoller J, Reum T, Roots I (1997) Deficiency of glutathione S-transferases T1 and M1 as heritable factors of increased cutaneous UV sensitivity. J Invest Dermatol 108:229-232
Ketterer B, Taylor J, Meyer D et al (1993) Some functions of glutathione transferase. In: Tew K et al (eds) Structure and function of glutathione transferase. CRC Press, Boca Raton, pp 15-27
Keyse SM (1993) The induction of gene expression in mammalian cells by radiation. Semin Cancer Biol 4:119-128
Kim KH, Park GT, Lim YB, Rue SW, Jung JC, Sonn JK, Bae YS, Park JW, Lee YS (2004) Expression of connective tissue growth factor, a biomarker in senescence of human diploid fibroblasts, is up-regulated by a transforming growth factor-beta-mediated signaling pathway. Biochem Biophys Res Commun 318:819-825
Kuroda K, Okamoto O, Shinkai H (1999) Dermatopontin expression is decreased in hypertrophic scar and systemic sclerosis skin fibroblasts and is regulated by transforming growth factor-beta1, interleukin-4, and matrix collagen. J Invest Dermatol 112:706-710
Lambert CA, Soudant EP, Nusgens BV, Lapiere CM (1992) Pretranslational regulation of extracellular matrix macromolecules and collagenase expression in fibroblasts by mechanical forces. Lab Invest 66:444-451
Leask A, Abraham DJ (2003) The role of connective tissue growth factor, a multifunctional matricellular protein, in fibroblast biology. Biochem Cell Biol 81:355-363
Lecka-Czernik B, Moerman EJ Jones RA, Goldstein S (1996) Identification of gene sequences overexpressed in senescent and Werner syndrome human fibroblasts. Exp Gerontol 31:159-174
Lener T, Moll PR, Rinnerthaler M, Bauer J, Aberger F, Richter K (2006) Expression profiling of aging in the human skin. Exp Gerontol 41:387-397
Ly DH, Lockhart DJ, Lerner RA, Schultz PG (2000) Mitotic misregulation and human aging. Science 287:2486-2492
Ma W, Wlaschek M, Tantcheva-Poor I, Schneider LA, Naderi L, Razi-Wolf Z, Schuller J, Scharffetter-Kochanek K (2001) Chronological ageing and photoageing of the fibroblasts and the dermal connective tissue. Clin Exp Dermatol 26:592-599
Matthews E, Haimes E, Duguet AM, Clark BF, Swine C, Toussaint O (2005) Informed consent of very old patients and modern genomics. Biogerontology 6:81-84
Meewes C, Poswig A, Dissemond J, Brenneisen P, Scharffetter-Kochanek K (2000) Adaptive antioxidant defence in human dermal fibroblasts. Br J Dermatol 143:662-663
Norton JD (2000) ID helix-loop-helix proteins in cell growth, differentiation and tumorigenesis. J Cell Sci 113(Pt 22):3897-3905
Okamoto O, Fujiwara S, Abe M, Sato Y (1999) Dermatopontin interacts with transforming growth factor beta and enhances its biological activity. Biochem J 337(Pt 3):537-541
Pascal T, Debacq-Chainiaux F, Chretien A, Bastin C, Dabee AF, Bertholet V, Remacle J, Toussaint O (2005) Comparison of replicative senescence and stress-induced premature senescence combining differential display and low-density DNA arrays. FEBS Lett 579:3651-3659
Patterson TA, Lobenhofer EK, Fulmer-Smentek SB, Collins PJ, Chu TM, Bao W, Fang H, Kawasaki ES, Hager J, Tikhonova IR, Walker SJ, Zhang L, Hurban P, de Longueville F, Fuscoe JC, Tong W, Shi L, Wolfinger RD (2006) Performance comparison of one-color and two-color platforms within the MicroArray Quality Control (MAQC) project. Nat Biotechnol 24:1140-1150
Petri JB, Rott O, Wetzig T, Herrmann K, Haustein UF (1999) The small proteoglycan fibromodulin is expressed in mitotic, but not in postmitotic fibroblasts. Mol Cell Biol Res Commun 1:59-65
Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29:e45
Pfaffl MW, Horgan GW, Dempfle L (2002) Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res 30:e36
Polsky D, Young AZ, Busam KJ, Alani RM (2001) The transcriptional repressor of p16/Ink4a, Id1, is up-regulated in early melanomas. Cancer Res 61:6008-6011
Quan T, He T, Kang S, Voorhees JJ, Fisher GJ (2002a) Connective tissue growth factor: Expression in human skin in vivo and inhibition by ultraviolet irradiation. J Invest Dermatol 118:402-408
Quan T, He T, Kang S, Voorhees JJ, Fisher GJ (2002b) Ultraviolet irradiation alters transforming growth factor beta/smad pathway in human skin in vivo. J Invest Dermatol 119:499-506
Rittie L, Fisher GJ (2002) UV-light-induced signal cascades and skin aging. Ageing Res Rev 1:705-720
Saeed AI, Sharov V, White J, Li J, Liang W, Bhagabati N, Braisted J, Klapa M, Currier T, Thiagarajan M, Sturn A, Snuffin M, Rezantsev A, Popov D, Ryltsov A, Kostukovich E, Borisovsky I, Liu Z, Vinsavich A, Trush V, Quackenbush J (2003) TM4: A free, open-source system for microarray data management and analysis. Biotechniques 34:374-378
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 35:307-316
Seo JY, Kim EK, Lee SH, Park KC, Kim KH, Eun HC, Chung JH (2003) Enhanced expression of cylooxygenase-2 by UV in aged human skin in vivo. Mech Ageing Dev 124:903-910
Shi L, Reid LH, Jones WD, Shippy R, Warrington JA, Baker SC, Collins PJ, de Longueville F, Kawasaki ES, Lee KY, Luo Y, Sun YA, Willey JC, Setterquist RA, Fischer GM, Tong W, Dragan YP, Dix DJ, Frueh FW, Goodsaid FM, Herman D, Jensen RV, Johnson CD, Lobenhofer EK, Puri RK, Schrf U, Thierry-Mieg J, Wang C, Wilson M, Wolber PK, Zhang L, Amur S, Bao W, Barbacioru CC, Lucas AB, Bertholet V, Boysen C, Bromley B, Brown D, Brunner A, Canales R, Cao XM, Cebula TA, Chen JJ, Cheng J, Chu TM, Chudin E, Corson J, Corton JC, Croner LJ, Davies C, Davison TS, Delenstarr G, Deng X, Dorris D, Eklund AC, Fan XH, Fang H, Fulmer-Smentek S, Fuscoe JC, Gallagher K, Ge W, Guo L, Guo X, Hager J, Haje PK, Han J, Han T, Harbottle HC, Harris SC, Hatchwell E, Hauser CA, Hester S, Hong H, Hurban P, Jackson SA, Ji H, Knight CR, Kuo WP, LeClerc JE, Levy S, Li QZ, Liu C, Liu Y, Lombardi MJ, Ma Y, Magnuson SR, Maqsodi B, McDaniel T, Mei N, Myklebost O, Ning B, Novoradovskaya N, Or MS, Osborn TW, Papallo A, Patterson TA, Perkins RG, Peters EH, Peterson R et al (2006) The MicroArray Quality Control (MAQC) project shows inter- and intraplatform reproducibility of gene expression measurements. Nat Biotechnol 24:1151-1161
Shigenaga MK, Hagen TM, Ames BN (1994) Oxidative damage and mitochondrial decay in aging. Proc Natl Acad Sci USA 91:10771-10778
Shindo Y, Witt E, Han D, Packer L (1994) Dose-response effects of acute ultraviolet irradiation on antioxidants and molecular markers of oxidation in murine epidermis and dermis. J Invest Dermatol 102:470-475
Uitto J (1986) Connective tissue biochemistry of the aging dermis. Age-related alterations in collagen and elastin. Dermatol Clin 4:433-446
Wlaschek M, Tantcheva-Poor I, Naderi L, Ma W, Schneider LA, Razi-Wolf Z, Schuller J, Scharffetter-Kochanek K (2001) Solar UV irradiation and dermal photoaging. J Photochem Photobiol B 63:41-51
Yoon IK, Kim HK, Kim YK, Song IH, Kim W, Kim S, Baek SH, Kim JH, Kim JR (2004) Exploration of replicative senescence-associated genes in human dermal fibroblasts by cDNA microarray technology. Exp Gerontol 39:1369-1378
Zdanov S, Debacq-Chainiaux F, Remacle J, Toussaint O (2006) Identification of p38MAPK-dependent genes with changed transcript abundance in H2O2-induced premature senescence of IMR-90 hTERT human fibroblasts. FEBS Lett 580:6455-6463
Zhang H, Rosdahl I (2003) Ultraviolet A and B differently induce intracellular protein expression in human skin melanocytes - a speculation of separate pathways in initiation of melanoma. Carcinogenesis 24:1929-1934