BibTex RIS Cite

Klotho gene, aging and DNA methylation

Year 2014, Volume: 4 Issue: 3, 182 - 192, 15.12.2014

Abstract

Aging is a natural process, which shows itself as anatomical and physiological changes in living organisms in the course of time. There are both environmental and genetic factors affecting the aging process. Within the genetic factors, several genes controlling different metabolic pathways involve in the aging process. Klotho (kl) gene, that is the subject of this review, is just one of genetic factors. Kl gene was first identified in mice and it was shown that dysfunction of this gene causes premature aging symptoms and short-lived of the mice. Recently, it was reported that kl gene could be epigenetically controlled by DNA methylation. In our unpublished study, we showed that DNMT enzymes have down-regulatory effects on human kl gene expression. We believe that elucidating the regulation mechanism of the human kl gene allows us more reliable methods to be followed for eliminating health problems that may arise due to low expression of Kl protein.

References

  • Herskind AM, McGue M, Holm NV, Sorensen TI, Harvald B, Vaupel J W. The heritability of human longevity: a population-based study of 2872 Danish twin pairs born 1870-1900. Hum Genet. 1996;97:319- 323.
  • Christensen K, Johnson TE, Vaupel JW. The quest for genetic determinants of human longevity: challenges and insights. Nat Rev Genet. 2006;7:436-448.
  • de Magalhaes JP, Cabral JA, Magalhaes D. The influence of genes on the aging process of mice: a statistical assessment of the genetics of aging. Genetics. 2005;169:265-274.
  • Masternak MM, Al-Regaiey KA, Del Rosario Lim MM, Jimenez-Ortega V, Panici JA, Bonkowski MS, Bartke A. Effects of caloric restriction on insulin pathway gene expression in the skeletal muscle and liver of normal and long-lived GHR-KO mice. Exp Gerontol. 2005;40:679-684.
  • Cabelof DC, Raffoul JJ, Ge Y, Van Remmen H, Matherly LH, Heydari AR. Age-related loss of the DNA repair response following exposure to oxidative stress. J Gerontol A Biol Sci Med Sci. 2006;61:427-434.
  • Kurosu H, Yamamoto M, Clark JD, Pastor JV, Nandi A, Gurnani P, McGuinness OP, Chikuda H, Yamaguchi M, Kawaguchi H, Shimomura I, Takayama Y, Herz J, Kahn CR, Rosenblatt KP, Kuro-o M. Suppression of aging in mice by the hormone Klotho. Science. 2005;309:1829- 1833.
  • Flurkey K, Papaconstantinou J, Miller RA, Harrison DE. Lifespan extension and delayed immune and collagen aging in mutant mice with defects in growth hormone production. Proc Natl Acad Sci U S A. 2001;98:6736-6741.
  • Giannakou ME, Goss M, Junger MA, Hafen E, Leevers SJ, Partridge L. Long-lived Drosophila with overexpressed dFOXO in adult fat body. Science. 2004;305:361.
  • Dupont J, Holzenberger M. IGF type 1 receptor: a cell cycle progression factor that regulates aging. Cell Cycle 2003;2:270-272.
  • Dupont J, Holzenberger M. Biology of insulin-like growth factors in development. Birth Defects Res C Embryo Today. 2003;69:257-271.
  • Tyner SD, Venkatachalam S, Choi J, Jones S, Ghebranious N, Igelmann H, Lu X, Soron G, Cooper B, Brayton C, Park SH, Thompson T, Karsenty G, Bradley A, Donehower L.A. p53 mutant mice that display early ageing-associated phenotypes. Nature. 2002;415:45-53.
  • Barbieri M, Bonafe M, Franceschi C, Paolisso G. Insulin/IGF-I-signaling pathway: an evolutionarily conserved mechanism of longevity from yeast to humans. Am J Physiol Endocrinol Metab. 2003;285:E1064- 1071.
  • Castro E, Edland SD, Lee L, Ogburn CE, Deeb SS, Brown G, Panduro A, Riestra R, Tilvis R, Louhija J, Penttinen R, Erkkola R, Wang L, Martin GM, Oshima J. Polymorphisms at the Werner locus: II. 1074Leu/ Phe, 1367Cys/Arg, longevity, and atherosclerosis. Am J Med Genet. 2000;95:374-380.
  • Flachsbart F, Caliebe A, Kleindorp R, Blanche H, von Eller-Eberstein H, Nikolaus S, Schreiber S, Nebel A. Association of FOXO3A variation with human longevity confirmed in German centenarians. Proc Natl Acad Sci U S A. 2009;106:2700-2705.
  • van Heemst D, Beekman M, Mooijaart SP, Heijmans BT, Brandt BW, Zwaan BJ, Slagboom PE, Westendorp RG. Reduced insulin/IGF-1 signalling and human longevity. Aging Cell. 2005;4:79-85.
  • Donehower LA. p53: guardian AND suppressor of longevity? Exp Gerontol. 2005;40:7-9.
  • Willcox BJ, Donlon TA, He Q, Chen R, Grove JS, Yano K, Masaki KH, Willcox DC, Rodriguez B, Curb JD. FOXO3A genotype is strongly associated with human longevity. Proc Natl Acad Sci U S A. 2008;105:13987-13992.
  • Kim JY, Jung KJ, Choi JS, Chung HY. Modulation of the age-related nuclear factor-kappaB (NF-kappaB) pathway by hesperetin. Aging Cell. 2006;5:401-411.
  • Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T, Ohyama Y, Kurabayashi M, Kaname T, Kume E, Iwasaki H, Iida A, Shiraki-Iida T, Nishikawa S, Nagai R, Nabeshima YI. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature. 1997;390:45-51.
  • Matsumura Y, Aizawa H, Shiraki-Iida T, Nagai R, Kuro-o M, Nabeshima Y. Identification of the human klotho gene and its two transcripts encoding membrane and secreted klotho protein. Biochem Biophys Res Commun. 1998;242:626-630.
  • Arking DE, Krebsova A, Macek M, Macek, M, Arking A, Mian IS, Fried L, Hamosh A, Dey S, McIntosh I, Dietz HC. Association of human aging with a functional variant of klotho. Proc Natl Acad Sci U S A.
  • Arking DE, Becker DM, Yanek LR, Fallin D, Judge DP, Moy TF, Becker LC, Dietz HC. KLOTHO allele status and the risk of early-onset occult coronary artery disease. Am J Hum Genet. 2003;72:1154-1161.
  • Ohyama Y, Kurabayashi M, Masuda H, Nakamura T, Aihara Y, Kaname T, Suga T, Arai M, Aizawa H, Matsumura Y, Kuro-o M, Nabeshima Y, Nagail, R. Molecular cloning of rat klotho cDNA: markedly decreased expression of klotho by acute inflammatory stress. Biochem Biophys Res Commun. 1998;251:920-925.
  • Shiraki-Iida T, Aizawa H, Matsumura Y, Sekine S, Iida A, Anazawa H, Nagai R, Kuro-o M, Nabeshima Y. Structure of the mouse klotho gene and its two transcripts encoding membrane and secreted protein. FEBS Lett. 1998;424:6-10.
  • Tohyama O, Imura A, Iwano A, Freund JN, Henrissat B, Fujimori T, Nabeshima Y. Klotho is a novel beta-glucuronidase capable of hydrolyzing steroid beta-glucuronides. J Biol Chem. 2004;279:9777- 9784.
  • Wang Y, Sun Z. Current understanding of klotho, Ageing Res Rev 2009; 8: 43-51.
  • Chen CD, Podvin S, Gillespie E, Leeman SE, Abraham CR. Insulin stimulates the cleavage and release of the extracellular domain of Klotho by ADAM10 and ADAM17. Proc Natl Acad Sci U S A. 2007;104:19796-19801.
  • Kamemori M, Ohyama Y, Kurabayashi M, Takahashi K, Nagai R, Furuya N. Expression of Klotho protein in the inner ear. Hear Res. 2002;171:103-110.
  • Li SA, Watanabe M, Yamada H, Nagai A, Kinuta M, Takei K. Immunohistochemical localization of Klotho protein in brain, kidney, and reproductive organs of mice. Cell Struct Funct. 2004;29:91-99.
  • Imura A, Iwano A, Tohyama O, Tsuji Y, Nozaki K, Hashimoto N, Fujimori T, Nabeshima Y. Secreted Klotho protein in sera and CSF: implication for post-translational cleavage in release of Klotho protein from cell membrane. FEBS Lett. 2004;565:143-147.
  • Kuro-o, M. Klotho as a regulator of oxidative stress and senescence. Biol Chem. 2008;389:233-241.
  • Zhu D, Mackenzie NC, Millan JL, Farquharson C, MacRae VE. A protective role for FGF-23 in local defence against disrupted arterial wall integrity? Mol Cell Endocrinol. 2013;372:1-11.
  • Urakawa I, Yamazaki Y, Shimada T, Iijima K, Hasegawa H, Okawa K, Fujita T, Fukumoto S, Yamashita T. Klotho converts canonical FGF receptor into a specific receptor for FGF23. Nature. 2006;444:770-774.
  • Liu S, Quarles LD. How fibroblast growth factor 23 works. J Am Soc Nephrol. 2007;18:1637-1647.
  • Kuro-o M. A potential link between phosphate and aging--lessons from Klotho-deficient mice. Mech Ageing Dev. 2010;131:270-275.
  • Hu MC, Shi M, Zhang J, Pastor J, Nakatani T, Lanske B, Razzaque MS, Rosenblatt KP, Baum MG, Kuro-o M, Moe OW. Klotho: a novel phosphaturic substance acting as an autocrine enzyme in the renal proximal tubule. FASEB J. 2010;24:3438-3450.
  • Chang Q, Hoefs S, van der Kemp AW, Topala CN, Bindels RJ, Hoenderop JG. The beta-glucuronidase klotho hydrolyzes and activates the TRPV5 channel. Science. 2005;310:490-493.
  • Liu H, Fergusson MM, Castilho RM, Liu J, Cao L, Chen J, Malide D, Rovira II, Schimel D, Kuo CJ, Gutkind JS, Hwang PM, Finkel T. Augmented Wnt signaling in a mammalian model of accelerated aging. Science. 2007;317:803-806.
  • Mitani H, Ishizaka N, Aizawa T, Ohno M, Usui S, Suzuki T, Amaki T, Mori I, Nakamura Y, Sato M, Nangaku M, Hirata Y, Nagai R. In vivo klotho gene transfer ameliorates angiotensin II-induced renal damage. Hypertension. 2002;39:838-843.
  • de Oliveira RM. Klotho RNAi induces premature senescence of human cells via a p53/p21 dependent pathway. FEBS Lett. 2006;580,5753-5758.
  • Haruna Y, Kashihara N, Satoh M, Tomita N, Namikoshi T, Sasaki T, Fujimori T, Xie P, Kanwar YS. Amelioration of progressive renal injury by genetic manipulation of Klotho gene. Proc Natl Acad Sci U S A. 2007;104:2331-2336.
  • Tsujikawa H, Kurotaki Y, Fujimori T, Fukuda K, Nabeshima Y. Klotho, a gene related to a syndrome resembling human premature aging, functions in a negative regulatory circuit of vitamin D endocrine system. Mol Endocrinol. 2003;17:2393-2403.
  • Silver J, Naveh-Many T. FGF23 and the parathyroid glands. Pediatr Nephrol. 2010;25:2241-2245.
  • Turan K, Ata P. Effects of intra- and extracellular factors on anti-aging klotho gene expression. Genet Mol Res. 2011;10:2009-2023.
  • Lee J, Jeong DJ, Kim J, Lee S, Park JH, Chang B, Jung SI, Yi L, Han Y, Yang Y, Kim KI, Lim JS, Yang I, Jeon S, Bae DH, Kim CJ, Lee MS. The anti-aging gene KLOTHO is a novel target for epigenetic silencing in human cervical carcinoma. Mol Cancer. 2010;9:109.
  • Çağlayan E. (2014) DNA Metil Transferaz Enzimlerinin Yaşlanma İle İlgili İnsan Klotho Geni Anlatımı Üzerine Etkilerinin Araştırılması. M.Ü. Sağlık Bilimleri Enstitüsü YLT, İ., (Danışman: Prof. Dr. K.Turan).
  • Waddington CH. The epigenotype. 1942. Int J Epidemiol. 2012;41:10- 13.
  • Ducasse M, Brown MA. Epigenetic aberrations and cancer. Mol Cancer. 2006;5:60.
  • Gigek CO, Chen ES, Calcagno DQ, Wisnieski F, Burbano RR, Smith MA. Epigenetic mechanisms in gastric cancer. Epigenomics. 2012;4:279- 294.
  • Chin SP, Dickinson JL, Holloway AF. Epigenetic regulation of prostate cancer. Clin Epigenetics. 2011;2:151-169.
  • Rubinek T, Shulman M, Israeli S, Bose S, Avraham A, Zundelevich A, Evron E, Gal-Yam EN, Kaufman B, Wolf I. Epigenetic silencing of the tumor suppressor klotho in human breast cancer. Breast Cancer Res Treat. 2012;133:649-657.
  • Catalano MG, Fortunati N, Boccuzzi G. Epigenetics modifications and therapeutic prospects in human thyroid cancer. Front Endocrinol (Lausanne) 2012; 3: 40.
  • Enokida H, Nakagawa M. Epigenetics in bladder cancer. Int J Clin Oncol. 2008;13:298-307.
  • Dubuc AM, Mack S, Unterberger A, Northcott PA, Taylor MD. The epigenetics of brain tumors. Methods Mol Biol. 2012;863:139-153.
  • Khare S, Verma M. Epigenetics of colon cancer. Methods Mol Biol.
  • Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G, Tonti-Filippini J, Nery JR, Lee L, Ye Z, Ngo QM, Edsall L, Antosiewicz-Bourget J, Stewart R, Ruotti V, Millar AH, Thomson JA, Ren B, Ecker JR. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature. 2009;462:315-322.
  • Goldberg AD, Allis CD, Bernstein E. Epigenetics: a landscape takes shape. Cell. 2007;128:635-638.
  • Jurkowska RZ, Jurkowski TP, Jeltsch A. Structure and function of mammalian DNA methyltransferases. Chembiochem. 2011;12:206-222.
  • Kim JK, Samaranayake M, Pradhan S. Epigenetic mechanisms in mammals. Cell Mol Life Sci. 2009;66:596-612.
  • Bird A. The essentials of DNA methylation. Cell. 1992;70:5-8.
  • Otto SP, Walbot V. DNA methylation in eukaryotes: kinetics of demethylation and de novo methylation during the life cycle. Genetics. 1990;124:429-437.
  • Pradhan S, Bacolla A, Wells RD, Roberts RJ. Recombinant human DNA (cytosine-5) methyltransferase. I. Expression, purification, and comparison of de novo and maintenance methylation. J Biol Chem. 1999;274:33002-33010.
  • Gruenbaum Y, Cedar H, Razin, A. Substrate and sequence specificity of a eukaryotic DNA methylase. Nature. 1982;295:620-622.
  • Spada F, Haemmer A, Kuch D, Rothbauer U, Schermelleh L, Kremmer E, Carell T, Langst G, Leonhardt H. DNMT1 but not its interaction with the replication machinery is required for maintenance of DNA methylation in human cells. J Cell Biol. 2007;176:565-571.
  • Robertson KD. DNA methylation and chromatin - unraveling the tangled web. Oncogene. 2002;21:5361-5379.
  • Okano M, Xie S, Li E. Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases. Nat Genet. 1998;19:219-220.
  • Xie S, Wang Z, Okano M, Nogami M, Li Y, He WW, Okumura K, Li E. Cloning, expression and chromosome locations of the human DNMT3 gene family. Gene. 1999;236:87-95.
  • Wolf I, Levanon-Cohen S, Bose S, Ligumsky H, Sredni B, Kanety H, Kuro-o M, Karlan B, Kaufman B, Koeffler HP, Rubinek T. Klotho: a tumor suppressor and a modulator of the IGF-1 and FGF pathways in human breast cancer. Oncogene. 2008;27:7094-7105.
  • Wang L, Wang X, Wang X, Jie P, Lu H, Zhang S, Lin X, Lam EK, Cui Y, Yu J, Jin H. Klotho is silenced through promoter hypermethylation in gastric cancer. Am J Cancer Res. 2011;1:111-119.
  • Pan J, Zhong J, Gan LH, Chen SJ, Jin HC, Wang X, Wang LJ. Klotho, an anti-senescence related gene, is frequently inactivated through promoter hypermethylation in colorectal cancer. Tumour Biol. 2011;32:729-735.
  • Sun CY, Chang SC, Wu MS. Suppression of Klotho expression by protein-bound uremic toxins is associated with increased DNA methyltransferase expression and DNA hypermethylation. Kidney Int. 2012;81:640-650.
  • Kulis M, Esteller M. DNA methylation and cancer. Adv Genet. 2010;70:27-56.
  • Moreno JA, Izquierdo MC, Sanchez-Nino MD, Suarez-Alvarez B, Lopez- Larrea C, Jakubowski A, Blanco J, Ramirez R, Selgas R, Ruiz-Ortega M, Egido J, Ortiz A, Sanz AB. The inflammatory cytokines TWEAK and TNFalpha reduce renal klotho expression through NFkappaB. J Am Soc Nephrol. 2011;22:1315-1325.
  • Zhang H, Li Y, Fan Y, Wu J, Zhao B, Guan Y, Chien S, Wang N. Klotho is a target gene of PPAR-gamma. Kidney Int. 2008;74:732-739.
  • King GD, Chen C, Huang MM, Zeldich E, Brazee PL, Schuman ER, Robin M, Cuny GD, Glicksman MA, Abraham CR. Identification of novel small molecules that elevate Klotho expression. Biochem J. 2012;441:453- 461.
  • Hernandez DG, Nalls MA, Gibbs JR, Arepalli S, van der Brug M, Chong S, Moore M, Longo DL, Cookson MR, Traynor BJ, Singleton AB. Distinct DNA methylation changes highly correlated with chronological age in the human brain. Hum Mol Genet. 2011;20:1164-1172.
  • Siegmund KD, Connor CM, Campan M, Long TI, Weisenberger DJ, Biniszkiewicz D, Jaenisch R, Laird PW, Akbarian S. DNA methylation in the human cerebral cortex is dynamically regulated throughout the life span and involves differentiated neurons. PLoS One. 2007;2:e895.
  • King GD, Rosene DL, Abraham CR. Promoter methylation and age- related downregulation of Klotho in rhesus monkey. Age (Dordr). 2012;34:1405-1419.

Klotho geni, yaşlanma ve DNA metilasyonu

Year 2014, Volume: 4 Issue: 3, 182 - 192, 15.12.2014

Abstract

Doğal bir süreç olan yaşlanma, zamanın akışı içerisinde canlı organizmada görülen anatomik ve fizyolojik değişiklikler olarak kendini gösterir. Yaşlanma sürecinde hem çevresel hem de genetik faktörler etkili olur. Genetik faktörler arasında farklı metabolik yolakları kontrol eden birçok gen yer alır. Bu derlemede ele alınan Klotho (kl) geni bunlardan sadece biridir. Kl geni ilk kez farelerde saptanmış ve bu genin işlev görememesi halinde erken yaşlanma belirtilerinin ortaya çıktığı ve farelerin kısa ömürlü olduğu görülmüştür. Yakın tarihli çalışmalar kl geni anlatımının DNA metilasyonu ile epigenik olarak kontrol edildiği yönünde sonuçlar ortaya koymaktadır. Henüz yayınlanmamış bir çalışmamızda da DNMT enzimlerinin insan kl geni anlatımı üzerinde baskılayıcı etkiye sahip olduğu saptanmıştır. İnsan kl geninin işleyiş mekanizmasının aydınlatılmasının, Kl proteininin anlatım düzeyine bağlı olarak ortaya çıkabilecek sağlık problemlerinin giderilmesinde daha güvenilir yöntemlerin izlenmesine olanak sağlayacağı kanısındayız.

References

  • Herskind AM, McGue M, Holm NV, Sorensen TI, Harvald B, Vaupel J W. The heritability of human longevity: a population-based study of 2872 Danish twin pairs born 1870-1900. Hum Genet. 1996;97:319- 323.
  • Christensen K, Johnson TE, Vaupel JW. The quest for genetic determinants of human longevity: challenges and insights. Nat Rev Genet. 2006;7:436-448.
  • de Magalhaes JP, Cabral JA, Magalhaes D. The influence of genes on the aging process of mice: a statistical assessment of the genetics of aging. Genetics. 2005;169:265-274.
  • Masternak MM, Al-Regaiey KA, Del Rosario Lim MM, Jimenez-Ortega V, Panici JA, Bonkowski MS, Bartke A. Effects of caloric restriction on insulin pathway gene expression in the skeletal muscle and liver of normal and long-lived GHR-KO mice. Exp Gerontol. 2005;40:679-684.
  • Cabelof DC, Raffoul JJ, Ge Y, Van Remmen H, Matherly LH, Heydari AR. Age-related loss of the DNA repair response following exposure to oxidative stress. J Gerontol A Biol Sci Med Sci. 2006;61:427-434.
  • Kurosu H, Yamamoto M, Clark JD, Pastor JV, Nandi A, Gurnani P, McGuinness OP, Chikuda H, Yamaguchi M, Kawaguchi H, Shimomura I, Takayama Y, Herz J, Kahn CR, Rosenblatt KP, Kuro-o M. Suppression of aging in mice by the hormone Klotho. Science. 2005;309:1829- 1833.
  • Flurkey K, Papaconstantinou J, Miller RA, Harrison DE. Lifespan extension and delayed immune and collagen aging in mutant mice with defects in growth hormone production. Proc Natl Acad Sci U S A. 2001;98:6736-6741.
  • Giannakou ME, Goss M, Junger MA, Hafen E, Leevers SJ, Partridge L. Long-lived Drosophila with overexpressed dFOXO in adult fat body. Science. 2004;305:361.
  • Dupont J, Holzenberger M. IGF type 1 receptor: a cell cycle progression factor that regulates aging. Cell Cycle 2003;2:270-272.
  • Dupont J, Holzenberger M. Biology of insulin-like growth factors in development. Birth Defects Res C Embryo Today. 2003;69:257-271.
  • Tyner SD, Venkatachalam S, Choi J, Jones S, Ghebranious N, Igelmann H, Lu X, Soron G, Cooper B, Brayton C, Park SH, Thompson T, Karsenty G, Bradley A, Donehower L.A. p53 mutant mice that display early ageing-associated phenotypes. Nature. 2002;415:45-53.
  • Barbieri M, Bonafe M, Franceschi C, Paolisso G. Insulin/IGF-I-signaling pathway: an evolutionarily conserved mechanism of longevity from yeast to humans. Am J Physiol Endocrinol Metab. 2003;285:E1064- 1071.
  • Castro E, Edland SD, Lee L, Ogburn CE, Deeb SS, Brown G, Panduro A, Riestra R, Tilvis R, Louhija J, Penttinen R, Erkkola R, Wang L, Martin GM, Oshima J. Polymorphisms at the Werner locus: II. 1074Leu/ Phe, 1367Cys/Arg, longevity, and atherosclerosis. Am J Med Genet. 2000;95:374-380.
  • Flachsbart F, Caliebe A, Kleindorp R, Blanche H, von Eller-Eberstein H, Nikolaus S, Schreiber S, Nebel A. Association of FOXO3A variation with human longevity confirmed in German centenarians. Proc Natl Acad Sci U S A. 2009;106:2700-2705.
  • van Heemst D, Beekman M, Mooijaart SP, Heijmans BT, Brandt BW, Zwaan BJ, Slagboom PE, Westendorp RG. Reduced insulin/IGF-1 signalling and human longevity. Aging Cell. 2005;4:79-85.
  • Donehower LA. p53: guardian AND suppressor of longevity? Exp Gerontol. 2005;40:7-9.
  • Willcox BJ, Donlon TA, He Q, Chen R, Grove JS, Yano K, Masaki KH, Willcox DC, Rodriguez B, Curb JD. FOXO3A genotype is strongly associated with human longevity. Proc Natl Acad Sci U S A. 2008;105:13987-13992.
  • Kim JY, Jung KJ, Choi JS, Chung HY. Modulation of the age-related nuclear factor-kappaB (NF-kappaB) pathway by hesperetin. Aging Cell. 2006;5:401-411.
  • Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T, Ohyama Y, Kurabayashi M, Kaname T, Kume E, Iwasaki H, Iida A, Shiraki-Iida T, Nishikawa S, Nagai R, Nabeshima YI. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature. 1997;390:45-51.
  • Matsumura Y, Aizawa H, Shiraki-Iida T, Nagai R, Kuro-o M, Nabeshima Y. Identification of the human klotho gene and its two transcripts encoding membrane and secreted klotho protein. Biochem Biophys Res Commun. 1998;242:626-630.
  • Arking DE, Krebsova A, Macek M, Macek, M, Arking A, Mian IS, Fried L, Hamosh A, Dey S, McIntosh I, Dietz HC. Association of human aging with a functional variant of klotho. Proc Natl Acad Sci U S A.
  • Arking DE, Becker DM, Yanek LR, Fallin D, Judge DP, Moy TF, Becker LC, Dietz HC. KLOTHO allele status and the risk of early-onset occult coronary artery disease. Am J Hum Genet. 2003;72:1154-1161.
  • Ohyama Y, Kurabayashi M, Masuda H, Nakamura T, Aihara Y, Kaname T, Suga T, Arai M, Aizawa H, Matsumura Y, Kuro-o M, Nabeshima Y, Nagail, R. Molecular cloning of rat klotho cDNA: markedly decreased expression of klotho by acute inflammatory stress. Biochem Biophys Res Commun. 1998;251:920-925.
  • Shiraki-Iida T, Aizawa H, Matsumura Y, Sekine S, Iida A, Anazawa H, Nagai R, Kuro-o M, Nabeshima Y. Structure of the mouse klotho gene and its two transcripts encoding membrane and secreted protein. FEBS Lett. 1998;424:6-10.
  • Tohyama O, Imura A, Iwano A, Freund JN, Henrissat B, Fujimori T, Nabeshima Y. Klotho is a novel beta-glucuronidase capable of hydrolyzing steroid beta-glucuronides. J Biol Chem. 2004;279:9777- 9784.
  • Wang Y, Sun Z. Current understanding of klotho, Ageing Res Rev 2009; 8: 43-51.
  • Chen CD, Podvin S, Gillespie E, Leeman SE, Abraham CR. Insulin stimulates the cleavage and release of the extracellular domain of Klotho by ADAM10 and ADAM17. Proc Natl Acad Sci U S A. 2007;104:19796-19801.
  • Kamemori M, Ohyama Y, Kurabayashi M, Takahashi K, Nagai R, Furuya N. Expression of Klotho protein in the inner ear. Hear Res. 2002;171:103-110.
  • Li SA, Watanabe M, Yamada H, Nagai A, Kinuta M, Takei K. Immunohistochemical localization of Klotho protein in brain, kidney, and reproductive organs of mice. Cell Struct Funct. 2004;29:91-99.
  • Imura A, Iwano A, Tohyama O, Tsuji Y, Nozaki K, Hashimoto N, Fujimori T, Nabeshima Y. Secreted Klotho protein in sera and CSF: implication for post-translational cleavage in release of Klotho protein from cell membrane. FEBS Lett. 2004;565:143-147.
  • Kuro-o, M. Klotho as a regulator of oxidative stress and senescence. Biol Chem. 2008;389:233-241.
  • Zhu D, Mackenzie NC, Millan JL, Farquharson C, MacRae VE. A protective role for FGF-23 in local defence against disrupted arterial wall integrity? Mol Cell Endocrinol. 2013;372:1-11.
  • Urakawa I, Yamazaki Y, Shimada T, Iijima K, Hasegawa H, Okawa K, Fujita T, Fukumoto S, Yamashita T. Klotho converts canonical FGF receptor into a specific receptor for FGF23. Nature. 2006;444:770-774.
  • Liu S, Quarles LD. How fibroblast growth factor 23 works. J Am Soc Nephrol. 2007;18:1637-1647.
  • Kuro-o M. A potential link between phosphate and aging--lessons from Klotho-deficient mice. Mech Ageing Dev. 2010;131:270-275.
  • Hu MC, Shi M, Zhang J, Pastor J, Nakatani T, Lanske B, Razzaque MS, Rosenblatt KP, Baum MG, Kuro-o M, Moe OW. Klotho: a novel phosphaturic substance acting as an autocrine enzyme in the renal proximal tubule. FASEB J. 2010;24:3438-3450.
  • Chang Q, Hoefs S, van der Kemp AW, Topala CN, Bindels RJ, Hoenderop JG. The beta-glucuronidase klotho hydrolyzes and activates the TRPV5 channel. Science. 2005;310:490-493.
  • Liu H, Fergusson MM, Castilho RM, Liu J, Cao L, Chen J, Malide D, Rovira II, Schimel D, Kuo CJ, Gutkind JS, Hwang PM, Finkel T. Augmented Wnt signaling in a mammalian model of accelerated aging. Science. 2007;317:803-806.
  • Mitani H, Ishizaka N, Aizawa T, Ohno M, Usui S, Suzuki T, Amaki T, Mori I, Nakamura Y, Sato M, Nangaku M, Hirata Y, Nagai R. In vivo klotho gene transfer ameliorates angiotensin II-induced renal damage. Hypertension. 2002;39:838-843.
  • de Oliveira RM. Klotho RNAi induces premature senescence of human cells via a p53/p21 dependent pathway. FEBS Lett. 2006;580,5753-5758.
  • Haruna Y, Kashihara N, Satoh M, Tomita N, Namikoshi T, Sasaki T, Fujimori T, Xie P, Kanwar YS. Amelioration of progressive renal injury by genetic manipulation of Klotho gene. Proc Natl Acad Sci U S A. 2007;104:2331-2336.
  • Tsujikawa H, Kurotaki Y, Fujimori T, Fukuda K, Nabeshima Y. Klotho, a gene related to a syndrome resembling human premature aging, functions in a negative regulatory circuit of vitamin D endocrine system. Mol Endocrinol. 2003;17:2393-2403.
  • Silver J, Naveh-Many T. FGF23 and the parathyroid glands. Pediatr Nephrol. 2010;25:2241-2245.
  • Turan K, Ata P. Effects of intra- and extracellular factors on anti-aging klotho gene expression. Genet Mol Res. 2011;10:2009-2023.
  • Lee J, Jeong DJ, Kim J, Lee S, Park JH, Chang B, Jung SI, Yi L, Han Y, Yang Y, Kim KI, Lim JS, Yang I, Jeon S, Bae DH, Kim CJ, Lee MS. The anti-aging gene KLOTHO is a novel target for epigenetic silencing in human cervical carcinoma. Mol Cancer. 2010;9:109.
  • Çağlayan E. (2014) DNA Metil Transferaz Enzimlerinin Yaşlanma İle İlgili İnsan Klotho Geni Anlatımı Üzerine Etkilerinin Araştırılması. M.Ü. Sağlık Bilimleri Enstitüsü YLT, İ., (Danışman: Prof. Dr. K.Turan).
  • Waddington CH. The epigenotype. 1942. Int J Epidemiol. 2012;41:10- 13.
  • Ducasse M, Brown MA. Epigenetic aberrations and cancer. Mol Cancer. 2006;5:60.
  • Gigek CO, Chen ES, Calcagno DQ, Wisnieski F, Burbano RR, Smith MA. Epigenetic mechanisms in gastric cancer. Epigenomics. 2012;4:279- 294.
  • Chin SP, Dickinson JL, Holloway AF. Epigenetic regulation of prostate cancer. Clin Epigenetics. 2011;2:151-169.
  • Rubinek T, Shulman M, Israeli S, Bose S, Avraham A, Zundelevich A, Evron E, Gal-Yam EN, Kaufman B, Wolf I. Epigenetic silencing of the tumor suppressor klotho in human breast cancer. Breast Cancer Res Treat. 2012;133:649-657.
  • Catalano MG, Fortunati N, Boccuzzi G. Epigenetics modifications and therapeutic prospects in human thyroid cancer. Front Endocrinol (Lausanne) 2012; 3: 40.
  • Enokida H, Nakagawa M. Epigenetics in bladder cancer. Int J Clin Oncol. 2008;13:298-307.
  • Dubuc AM, Mack S, Unterberger A, Northcott PA, Taylor MD. The epigenetics of brain tumors. Methods Mol Biol. 2012;863:139-153.
  • Khare S, Verma M. Epigenetics of colon cancer. Methods Mol Biol.
  • Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G, Tonti-Filippini J, Nery JR, Lee L, Ye Z, Ngo QM, Edsall L, Antosiewicz-Bourget J, Stewart R, Ruotti V, Millar AH, Thomson JA, Ren B, Ecker JR. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature. 2009;462:315-322.
  • Goldberg AD, Allis CD, Bernstein E. Epigenetics: a landscape takes shape. Cell. 2007;128:635-638.
  • Jurkowska RZ, Jurkowski TP, Jeltsch A. Structure and function of mammalian DNA methyltransferases. Chembiochem. 2011;12:206-222.
  • Kim JK, Samaranayake M, Pradhan S. Epigenetic mechanisms in mammals. Cell Mol Life Sci. 2009;66:596-612.
  • Bird A. The essentials of DNA methylation. Cell. 1992;70:5-8.
  • Otto SP, Walbot V. DNA methylation in eukaryotes: kinetics of demethylation and de novo methylation during the life cycle. Genetics. 1990;124:429-437.
  • Pradhan S, Bacolla A, Wells RD, Roberts RJ. Recombinant human DNA (cytosine-5) methyltransferase. I. Expression, purification, and comparison of de novo and maintenance methylation. J Biol Chem. 1999;274:33002-33010.
  • Gruenbaum Y, Cedar H, Razin, A. Substrate and sequence specificity of a eukaryotic DNA methylase. Nature. 1982;295:620-622.
  • Spada F, Haemmer A, Kuch D, Rothbauer U, Schermelleh L, Kremmer E, Carell T, Langst G, Leonhardt H. DNMT1 but not its interaction with the replication machinery is required for maintenance of DNA methylation in human cells. J Cell Biol. 2007;176:565-571.
  • Robertson KD. DNA methylation and chromatin - unraveling the tangled web. Oncogene. 2002;21:5361-5379.
  • Okano M, Xie S, Li E. Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases. Nat Genet. 1998;19:219-220.
  • Xie S, Wang Z, Okano M, Nogami M, Li Y, He WW, Okumura K, Li E. Cloning, expression and chromosome locations of the human DNMT3 gene family. Gene. 1999;236:87-95.
  • Wolf I, Levanon-Cohen S, Bose S, Ligumsky H, Sredni B, Kanety H, Kuro-o M, Karlan B, Kaufman B, Koeffler HP, Rubinek T. Klotho: a tumor suppressor and a modulator of the IGF-1 and FGF pathways in human breast cancer. Oncogene. 2008;27:7094-7105.
  • Wang L, Wang X, Wang X, Jie P, Lu H, Zhang S, Lin X, Lam EK, Cui Y, Yu J, Jin H. Klotho is silenced through promoter hypermethylation in gastric cancer. Am J Cancer Res. 2011;1:111-119.
  • Pan J, Zhong J, Gan LH, Chen SJ, Jin HC, Wang X, Wang LJ. Klotho, an anti-senescence related gene, is frequently inactivated through promoter hypermethylation in colorectal cancer. Tumour Biol. 2011;32:729-735.
  • Sun CY, Chang SC, Wu MS. Suppression of Klotho expression by protein-bound uremic toxins is associated with increased DNA methyltransferase expression and DNA hypermethylation. Kidney Int. 2012;81:640-650.
  • Kulis M, Esteller M. DNA methylation and cancer. Adv Genet. 2010;70:27-56.
  • Moreno JA, Izquierdo MC, Sanchez-Nino MD, Suarez-Alvarez B, Lopez- Larrea C, Jakubowski A, Blanco J, Ramirez R, Selgas R, Ruiz-Ortega M, Egido J, Ortiz A, Sanz AB. The inflammatory cytokines TWEAK and TNFalpha reduce renal klotho expression through NFkappaB. J Am Soc Nephrol. 2011;22:1315-1325.
  • Zhang H, Li Y, Fan Y, Wu J, Zhao B, Guan Y, Chien S, Wang N. Klotho is a target gene of PPAR-gamma. Kidney Int. 2008;74:732-739.
  • King GD, Chen C, Huang MM, Zeldich E, Brazee PL, Schuman ER, Robin M, Cuny GD, Glicksman MA, Abraham CR. Identification of novel small molecules that elevate Klotho expression. Biochem J. 2012;441:453- 461.
  • Hernandez DG, Nalls MA, Gibbs JR, Arepalli S, van der Brug M, Chong S, Moore M, Longo DL, Cookson MR, Traynor BJ, Singleton AB. Distinct DNA methylation changes highly correlated with chronological age in the human brain. Hum Mol Genet. 2011;20:1164-1172.
  • Siegmund KD, Connor CM, Campan M, Long TI, Weisenberger DJ, Biniszkiewicz D, Jaenisch R, Laird PW, Akbarian S. DNA methylation in the human cerebral cortex is dynamically regulated throughout the life span and involves differentiated neurons. PLoS One. 2007;2:e895.
  • King GD, Rosene DL, Abraham CR. Promoter methylation and age- related downregulation of Klotho in rhesus monkey. Age (Dordr). 2012;34:1405-1419.
There are 78 citations in total.

Details

Primary Language Turkish
Journal Section Articles
Authors

Elif Çağlayan This is me

Kadir Turan

Publication Date December 15, 2014
Submission Date December 15, 2014
Published in Issue Year 2014 Volume: 4 Issue: 3

Cite

APA Çağlayan, E., & Turan, K. (2014). Klotho geni, yaşlanma ve DNA metilasyonu. Clinical and Experimental Health Sciences, 4(3), 182-192. https://doi.org/10.5455/musbed.20140826121007
AMA Çağlayan E, Turan K. Klotho geni, yaşlanma ve DNA metilasyonu. Clinical and Experimental Health Sciences. December 2014;4(3):182-192. doi:10.5455/musbed.20140826121007
Chicago Çağlayan, Elif, and Kadir Turan. “Klotho Geni, yaşlanma Ve DNA Metilasyonu”. Clinical and Experimental Health Sciences 4, no. 3 (December 2014): 182-92. https://doi.org/10.5455/musbed.20140826121007.
EndNote Çağlayan E, Turan K (December 1, 2014) Klotho geni, yaşlanma ve DNA metilasyonu. Clinical and Experimental Health Sciences 4 3 182–192.
IEEE E. Çağlayan and K. Turan, “Klotho geni, yaşlanma ve DNA metilasyonu”, Clinical and Experimental Health Sciences, vol. 4, no. 3, pp. 182–192, 2014, doi: 10.5455/musbed.20140826121007.
ISNAD Çağlayan, Elif - Turan, Kadir. “Klotho Geni, yaşlanma Ve DNA Metilasyonu”. Clinical and Experimental Health Sciences 4/3 (December 2014), 182-192. https://doi.org/10.5455/musbed.20140826121007.
JAMA Çağlayan E, Turan K. Klotho geni, yaşlanma ve DNA metilasyonu. Clinical and Experimental Health Sciences. 2014;4:182–192.
MLA Çağlayan, Elif and Kadir Turan. “Klotho Geni, yaşlanma Ve DNA Metilasyonu”. Clinical and Experimental Health Sciences, vol. 4, no. 3, 2014, pp. 182-9, doi:10.5455/musbed.20140826121007.
Vancouver Çağlayan E, Turan K. Klotho geni, yaşlanma ve DNA metilasyonu. Clinical and Experimental Health Sciences. 2014;4(3):182-9.

14639   14640