{"id":5688,"date":"2014-01-20T20:19:28","date_gmt":"2018-12-15T14:59:59","guid":{"rendered":"https:\/\/gerec.fi\/tutkimus\/terveys-toimintakykyisyys-pitkaikaisyys-ja-biologinen-vanheneminen\/the-finnish-twin-study-on-ageing-fitsa-taina-rantanen-4\/"},"modified":"2024-06-19T08:42:26","modified_gmt":"2024-06-19T05:42:26","slug":"aging-of-the-immune-system","status":"publish","type":"page","link":"https:\/\/www.gerec.fi\/en\/research\/health\/aging-of-the-immune-system\/","title":{"rendered":"Aging of the immune system: cellular and molecular mechanisms \/ Mikko Hurme","raw":"Aging of the immune system: cellular and molecular mechanisms \/ Mikko Hurme"},"content":{"rendered":"[vc_row][vc_column][vc_column_text]Aging of the immune system: cellular and molecular mechanisms<\/span><\/p>\n

The function of the immune system in humans is severely compromised in elderly individuals leading to an increased frequency and severity of infectious diseases. In addition to this, it is associated with a low-degree inflammation, called inflammaging, which is in the background of several aging-associated phenotypic changes, e.g. frailty. During the last 5-7 years, we have characterized the aging-associated changes in the transcriptome, their functional consequences and possible regulatory factors. The focus has been in the epigenetics, i.e. mechanisms mediating the effect of environment and life-style factors on the activation of the genes. At present, the focus is on the following projects i) Viruses and immunosenescence. This far, only one virus, cytomegalovirus, is known to cause an exhaustion of the immune system. To analyze whether other viruses would have similar functions, the whole virome in the elderly individuals is characterized (using metagenomic and metatranscriptomic analyses) ii) Is there a \u201crejuvenating\u201d factor in the plasma of young individuals? Already several decades ago, the parabiosis approaches in animal models suggested that this would be the case ii) Genetics of longevity. This project (as well as the epigenetic epidemiology projects) are continued by participating in international meta-analyses.<\/p>\n

For these projects, the Vitality 90+ cohorts where biological samples are available are used. The techniques required have already been used in our previous publications.<\/p>\n

Research funding<\/span>
\nPirkanmaa Hospital District
\nCancer Society of Finland
\nThe Finnish Cultural Foundation
\nTampere Tuberculosis Foundation<\/p>\n

Research group<\/span>
\nPrincipal investigator
\nProfessor Mikko Hurme, mikko.hurme@tuni.fi<\/a><\/p>\n

Doctoral students
\nTapio Nevalainen, tapio.nevalainen@tuni.fi<\/a>
\nArttu Autio, arttu.autio@tuni.fi<\/a><\/p>\n

Selected publications 2016\u20132019<\/span><\/p>\n

Kananen L, Marttila S, Nevalainen T, Kummola L, Junttila I, Mononen N, K\u00e4h\u00f6nen M, Raitakari OT, Hervonen A, Jylh\u00e4 M, Lehtim\u00e4ki T, Hurme M<\/strong>, Jylh\u00e4v\u00e4 J. The trajectory of the blood DNA methylome aging rate largely\u00a0 set before adulthood: evidence from two longitudinal studies. AGE 38, 65, 2016.<\/p>\n

Kananen L, Marttila S, Nevalainen T, Jylh\u00e4v\u00e4 J, Mononen N, K\u00e4h\u00f6nen M, Raitakari OT, Lehtim\u00e4ki T, Hurme M<\/strong>. Aging-associated DNA methylation changes in middle-aged individuals: the Young Finns Study. BMC Genomics 17, 103, 2016.<\/p>\n

Jylh\u00e4v\u00e4 J, Kananen L, Raitanen J, Marttila S, Nevalainen T, Hervonen A, Jylh\u00e4 M, Hurme M<\/strong>. Methylomic predictors demonstrate the role of NF-kB in old-age mortality and are unrelated to the aging-associated epigenetic drift. Oncotarget 7, 19228, 2016.<\/p>\n

Ciccarone F, Malavolta M, Calabrese R, Guastafierro T,\u00a0 Bacalini NG, Reale A, Franceschi C, Capri M, Hervonen A, Hurme M<\/strong>, Grubeck-Loebenstein B, Koller B, Bernhardt J, Sch\u00f6n C, Slaagboom E, Touissant O, Sikora E, Gonos ES, Breusing N, Grune T, Jansen E, Dolle M, Moreno-Villanueva M, Sindlinger T, Burkle A, Zampieri M, Caiafa P. Age-dependent expression of DNMT1 and DNMT3B in PBMCs from a large European population enrolled in the MARK-AGE study. Aging Cell 15, 755, 2016.<\/p>\n

Nevalainen T, Kananen L, Marttila S, Jylh\u00e4v\u00e4 J, Mononen N, K\u00e4h\u00f6nen M, Raitakari OT, Hervonen A, Jylh\u00e4 M, Lehtim\u00e4ki T, Hurme M<\/strong>. Obesity accelerates epigenetic aging in middle-aged but not in elderly individuals. Clin Epigenetics 9, 20, 2017.<\/p>\n

Joshi PK, Pirastu N, Kentistou KA, Fischer K, Hofer E, Schraut KE, Clark DW, Nutile T, Barnes CLK, Timmers PRHJ, Shen X, Gandin I, McDaid AF, Folkman Hansen T,\u00a0 Gordon SD, Giulianini F, Boutin TS, Abdelaoui A, Zhao W, Medina-Gomez C, Bartz TM, Trompet S, Lange LA, Raffield L, van der Spek A, Galesloot TE, Proitsi P, Yanek LR, Bielak LF, Payton A, Murgia F, Pina Concas M, Biino G, Tajuddin SM, Sepp\u00e4l\u00e4 I, Amin N, Boerwinkle E, Borglum AD, Campbell A, Demerath EW, Demuth I, Faul JD, Ford I, Gialluisi A, G\u00f6gele M, Graff M, Hingorani A, Hottenga J, Hougaard DM, Hurme M<\/strong>, Ikram MA, Jylh\u00e4 M, Kuh D, Ligthart L, Lill CM, Lindenberger U, Lumley T, M\u00e4gi T, Margues-Vidal P, Medland C, Milani L, Nagy R, Ollier WR, Peyser PA, Pramstaller PP, Ridker PM, Rivadeneira F, Ruggiero D, Saba Y, Schmidt R, Schmidt H, Slaagbom PE, Smith BH, Smith JA, Sotoodehnia N, Steinhagen-Thiessen\u00a0 E, van Rooij FJA, Verbeek AL, Vermeulen SH, Vollenweider P, Wang Y, Werge T, Whitfield JB, Zonderman AB, Lehtim\u00e4ki T, Evans MK, Pirastu M, Fuchsberger C, Bertram L, Pendleton N, Kardia SLR, Ciullo M, Becker DM, Wong A, Psaty BM,\u00a0 van Duijn CM, Franceschini, North KE, Weir DW, Metspalu A, Boomsma DI, Hayward C, Chasman D, Martin NG, Sattar N, Campbell H, Esko T, Kutalik Z, Wilson JF. Genome-wide meta-analysis associates HLA-DQA1\/DRB1 and LPA and lifestyle factors with human longevity.\u00a0<\/strong>Nature Comm\u00a0 8, 610, 2017<\/p>\n

Nevalainen T, Autio A, Mishra B, Marttila S, Jylh\u00e4 M, Hurme M<\/strong>. Aging-associated patterns in the expression of human endogenous retroviruses. <\/strong>PLoS One 13, e0207407, 2018.<\/p>\n

Fiorito G, McCrory C, Robinson O, Carmeli C, Ochoa Rosales, C, Zhang Y, Colicino E, Dugue PA, Artaud F, McKay GJ, Jeong A, Mishra PP, Nost TH, Krogh V, Panico S, Sacerdote C, Tumino R, Palli D, Matullo G, Guarrera S, Gandini S, the BIOS Consortium, Bochud M, Dermitzakis E, Muka T, Schwartz J, Vokonas PS, Just A, Hodge AM, Giles GG, Southey MC, Hurme MA<\/strong>, Young I, McKnight AJ, Lund E, Baccarelli A, Milne R, Kenny RA, Elbaz A, Brenner H, Kee F, Voortman T, Probst-Hensch N, Lehtim\u00e4ki T, Elliot P, Stringhini S, Vineis P, Polodoro S, the Lifepath consortium. Socioeconomic position, lifestyle habits and biomarkers of epigenetic aging: a multi-cohort analysis. Aging in press.<\/p>\n

Mandaviya PR, Joehanes R, Brody J, Castillo-Fernandez JE, Dekkers KKF, Do AN, Graff M, H\u00e4nninen IK, Tanaka T, de Jonge EAL, Kiefte-de Jong JC, Anbsher DM, Aslibekyan S, de Rijke YB, Fornage M, Herbandez DG, Hurme MA<\/strong>, Ikram MA, Jacques PF, Justice AE, Kiel DP, Lemaitre RN, Mendelson MM, Mikkil\u00e4 V, Moore AZ, Pallister T, Raitakari OT, Schalkwijk CG, Sha J, Slagboom EP, Smith CE, Stehower CDA, Tsai PC, Uitterlinden AG, van der Kallen CJH, van Heemst DD, BIOS consortium, CHARGE consortium, Arnett DK, Bandinelli S, Bell JT, Heijmans BBT, Lehtim\u00e4ki T, Levy D, North KE, Sotoodehnia N, van Greevenbroek MMJ, van Meurs JBJ, Heil SG. Association of dietary folate and vitamin B12 intake with genome-wide DNA methylation in blood: a large scale epigenome-wide analysis of 5,841 individuals. Am J Clin Nutr in press<\/p>\n

Meryk A, Pangrazzi L, Hagen M, Hatzmann F, Jenewein B, Jakic B, Hermann-Kleiter N, Baier G, Jylh\u00e4v\u00e4 J, Hurme M<\/strong>, Trieb K, Grubeck-Loebenstein B. Fcm receptor as a new costimulatory molecule for T cells. Cell Rep in press<\/p>\n

Collaborators<\/span>
\nProfessor Marja Jylh\u00e4
\nProfessor Terho Lehtim\u00e4ki[\/vc_column_text][\/vc_column][\/vc_row]\n","protected":false,"raw":"[vc_row][vc_column][vc_column_text]Aging of the immune system: cellular and molecular mechanisms<\/span>\r\n\r\nThe function of the immune system in humans is severely compromised in elderly individuals leading to an increased frequency and severity of infectious diseases. In addition to this, it is associated with a low-degree inflammation, called inflammaging, which is in the background of several aging-associated phenotypic changes, e.g. frailty. During the last 5-7 years, we have characterized the aging-associated changes in the transcriptome, their functional consequences and possible regulatory factors. The focus has been in the epigenetics, i.e. mechanisms mediating the effect of environment and life-style factors on the activation of the genes. At present, the focus is on the following projects i) Viruses and immunosenescence. This far, only one virus, cytomegalovirus, is known to cause an exhaustion of the immune system. To analyze whether other viruses would have similar functions, the whole virome in the elderly individuals is characterized (using metagenomic and metatranscriptomic analyses) ii) Is there a \u201crejuvenating\u201d factor in the plasma of young individuals? Already several decades ago, the parabiosis approaches in animal models suggested that this would be the case ii) Genetics of longevity. This project (as well as the epigenetic epidemiology projects) are continued by participating in international meta-analyses.\r\n\r\nFor these projects, the Vitality 90+ cohorts where biological samples are available are used. The techniques required have already been used in our previous publications.\r\n\r\nResearch funding<\/span>\r\nPirkanmaa Hospital District\r\nCancer Society of Finland\r\nThe Finnish Cultural Foundation\r\nTampere Tuberculosis Foundation\r\n\r\nResearch group<\/span>\r\nPrincipal investigator\r\nProfessor Mikko Hurme, mikko.hurme@tuni.fi<\/a>\r\n\r\nDoctoral students\r\nTapio Nevalainen, tapio.nevalainen@tuni.fi<\/a>\r\nArttu Autio, arttu.autio@tuni.fi<\/a>\r\n\r\nSelected publications 2016\u20132019<\/span>\r\n\r\nKananen L, Marttila S, Nevalainen T, Kummola L, Junttila I, Mononen N, K\u00e4h\u00f6nen M, Raitakari OT, Hervonen A, Jylh\u00e4 M, Lehtim\u00e4ki T, Hurme M<\/strong>, Jylh\u00e4v\u00e4 J. The trajectory of the blood DNA methylome aging rate largely\u00a0 set before adulthood: evidence from two longitudinal studies. AGE 38, 65, 2016.\r\n\r\nKananen L, Marttila S, Nevalainen T, Jylh\u00e4v\u00e4 J, Mononen N, K\u00e4h\u00f6nen M, Raitakari OT, Lehtim\u00e4ki T, Hurme M<\/strong>. Aging-associated DNA methylation changes in middle-aged individuals: the Young Finns Study. BMC Genomics 17, 103, 2016.\r\n\r\nJylh\u00e4v\u00e4 J, Kananen L, Raitanen J, Marttila S, Nevalainen T, Hervonen A, Jylh\u00e4 M, Hurme M<\/strong>. Methylomic predictors demonstrate the role of NF-kB in old-age mortality and are unrelated to the aging-associated epigenetic drift. Oncotarget 7, 19228, 2016.\r\n\r\nCiccarone F, Malavolta M, Calabrese R, Guastafierro T,\u00a0 Bacalini NG, Reale A, Franceschi C, Capri M, Hervonen A, Hurme M<\/strong>, Grubeck-Loebenstein B, Koller B, Bernhardt J, Sch\u00f6n C, Slaagboom E, Touissant O, Sikora E, Gonos ES, Breusing N, Grune T, Jansen E, Dolle M, Moreno-Villanueva M, Sindlinger T, Burkle A, Zampieri M, Caiafa P. Age-dependent expression of DNMT1 and DNMT3B in PBMCs from a large European population enrolled in the MARK-AGE study. Aging Cell 15, 755, 2016.\r\n\r\nNevalainen T, Kananen L, Marttila S, Jylh\u00e4v\u00e4 J, Mononen N, K\u00e4h\u00f6nen M, Raitakari OT, Hervonen A, Jylh\u00e4 M, Lehtim\u00e4ki T, Hurme M<\/strong>. Obesity accelerates epigenetic aging in middle-aged but not in elderly individuals. Clin Epigenetics 9, 20, 2017.\r\n\r\nJoshi PK, Pirastu N, Kentistou KA, Fischer K, Hofer E, Schraut KE, Clark DW, Nutile T, Barnes CLK, Timmers PRHJ, Shen X, Gandin I, McDaid AF, Folkman Hansen T,\u00a0 Gordon SD, Giulianini F, Boutin TS, Abdelaoui A, Zhao W, Medina-Gomez C, Bartz TM, Trompet S, Lange LA, Raffield L, van der Spek A, Galesloot TE, Proitsi P, Yanek LR, Bielak LF, Payton A, Murgia F, Pina Concas M, Biino G, Tajuddin SM, Sepp\u00e4l\u00e4 I, Amin N, Boerwinkle E, Borglum AD, Campbell A, Demerath EW, Demuth I, Faul JD, Ford I, Gialluisi A, G\u00f6gele M, Graff M, Hingorani A, Hottenga J, Hougaard DM, Hurme M<\/strong>, Ikram MA, Jylh\u00e4 M, Kuh D, Ligthart L, Lill CM, Lindenberger U, Lumley T, M\u00e4gi T, Margues-Vidal P, Medland C, Milani L, Nagy R, Ollier WR, Peyser PA, Pramstaller PP, Ridker PM, Rivadeneira F, Ruggiero D, Saba Y, Schmidt R, Schmidt H, Slaagbom PE, Smith BH, Smith JA, Sotoodehnia N, Steinhagen-Thiessen\u00a0 E, van Rooij FJA, Verbeek AL, Vermeulen SH, Vollenweider P, Wang Y, Werge T, Whitfield JB, Zonderman AB, Lehtim\u00e4ki T, Evans MK, Pirastu M, Fuchsberger C, Bertram L, Pendleton N, Kardia SLR, Ciullo M, Becker DM, Wong A, Psaty BM,\u00a0 van Duijn CM, Franceschini, North KE, Weir DW, Metspalu A, Boomsma DI, Hayward C, Chasman D, Martin NG, Sattar N, Campbell H, Esko T, Kutalik Z, Wilson JF. Genome-wide meta-analysis associates HLA-DQA1\/DRB1 and LPA and lifestyle factors with human longevity.\u00a0<\/strong>Nature Comm\u00a0 8, 610, 2017\r\n\r\nNevalainen T, Autio A, Mishra B, Marttila S, Jylh\u00e4 M, Hurme M<\/strong>. Aging-associated patterns in the expression of human endogenous retroviruses. <\/strong>PLoS One 13, e0207407, 2018.\r\n\r\nFiorito G, McCrory C, Robinson O, Carmeli C, Ochoa Rosales, C, Zhang Y, Colicino E, Dugue PA, Artaud F, McKay GJ, Jeong A, Mishra PP, Nost TH, Krogh V, Panico S, Sacerdote C, Tumino R, Palli D, Matullo G, Guarrera S, Gandini S, the BIOS Consortium, Bochud M, Dermitzakis E, Muka T, Schwartz J, Vokonas PS, Just A, Hodge AM, Giles GG, Southey MC, Hurme MA<\/strong>, Young I, McKnight AJ, Lund E, Baccarelli A, Milne R, Kenny RA, Elbaz A, Brenner H, Kee F, Voortman T, Probst-Hensch N, Lehtim\u00e4ki T, Elliot P, Stringhini S, Vineis P, Polodoro S, the Lifepath consortium. Socioeconomic position, lifestyle habits and biomarkers of epigenetic aging: a multi-cohort analysis. Aging in press.\r\n\r\nMandaviya PR, Joehanes R, Brody J, Castillo-Fernandez JE, Dekkers KKF, Do AN, Graff M, H\u00e4nninen IK, Tanaka T, de Jonge EAL, Kiefte-de Jong JC, Anbsher DM, Aslibekyan S, de Rijke YB, Fornage M, Herbandez DG, Hurme MA<\/strong>, Ikram MA, Jacques PF, Justice AE, Kiel DP, Lemaitre RN, Mendelson MM, Mikkil\u00e4 V, Moore AZ, Pallister T, Raitakari OT, Schalkwijk CG, Sha J, Slagboom EP, Smith CE, Stehower CDA, Tsai PC, Uitterlinden AG, van der Kallen CJH, van Heemst DD, BIOS consortium, CHARGE consortium, Arnett DK, Bandinelli S, Bell JT, Heijmans BBT, Lehtim\u00e4ki T, Levy D, North KE, Sotoodehnia N, van Greevenbroek MMJ, van Meurs JBJ, Heil SG. Association of dietary folate and vitamin B12 intake with genome-wide DNA methylation in blood: a large scale epigenome-wide analysis of 5,841 individuals. Am J Clin Nutr in press\r\n\r\nMeryk A, Pangrazzi L, Hagen M, Hatzmann F, Jenewein B, Jakic B, Hermann-Kleiter N, Baier G, Jylh\u00e4v\u00e4 J, Hurme M<\/strong>, Trieb K, Grubeck-Loebenstein B. Fcm receptor as a new costimulatory molecule for T cells. Cell Rep in press\r\n\r\nCollaborators<\/span>\r\nProfessor Marja Jylh\u00e4\r\nProfessor Terho Lehtim\u00e4ki[\/vc_column_text][\/vc_column][\/vc_row]"},"excerpt":{"rendered":"[vc_row column_spacing=\"50\" bg_style=\"stretch\" css=\".vc_custom_1544814296502{padding-top: 30px !important;padding-bottom: 5px !important;}\"][vc_column][vc_column_text font_size=\"14px\"]Immuunisysteemin vanheneminen: solu- ja molekyylitason mekanismit Ihmisen immuunisysteemin toiminta heikkenee i\u00e4n my\u00f6t\u00e4 ja t\u00e4st\u00e4 on seurauksena vanhusten lis\u00e4\u00e4ntynyt sairastavuus ja kuolleisuus eri infektiotauteihin. Siihen liittyy my\u00f6s kohonnut tulehdusreaktio, ns. inflammaging, joka on…","protected":false,"raw":""},"author":1,"featured_media":0,"parent":5661,"menu_order":11,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_mi_skip_tracking":false,"_fi_post_content":"[vc_row column_spacing=\"50\" bg_style=\"stretch\" css=\".vc_custom_1544814296502{padding-top: 30px !important;padding-bottom: 5px !important;}\"][vc_column][vc_column_text font_size=\"14px\"]Immuunisysteemin vanheneminen: solu- ja molekyylitason mekanismit<\/span>\r\n\r\nIhmisen immuunisysteemin toiminta heikkenee i\u00e4n my\u00f6t\u00e4 ja t\u00e4st\u00e4 on seurauksena vanhusten lis\u00e4\u00e4ntynyt sairastavuus ja kuolleisuus eri infektiotauteihin. Siihen liittyy my\u00f6s kohonnut tulehdusreaktio, ns. inflammaging, joka on vastuussa esim. vanhusten hauraus\/raihnaus oireyhtym\u00e4st\u00e4.\u00a0 Olemme aikaisemmin kartoittaneet\u00a0 kaikki ne ihmisen geenit, joiden aktivaatiotaso muuttuu vanhetessa. Jatkotutkimuksissa selvitimme, miten epigeneettiset mekanismit (t.s. mekanismit, jotka muuttavat geenien toimintaa vaikuttamatta em\u00e4sj\u00e4rjestykseen) s\u00e4\u00e4telev\u00e4t n\u00e4iden geenien ilmenemist\u00e4. T\u00e4m\u00e4 on mahdollistanut ns. epigeneettisen kellon laskemisen (ns. biologinen ik\u00e4), joka korreloi hyvin eri vanhenemiseen liittyvien\u00a0 fenotyyppimuutosten ja kuolleisuuden kanssa. My\u00f6s varsinaisen genetiikan merkityst\u00e4 ihmisen pitk\u00e4ik\u00e4isyyden s\u00e4\u00e4telyss\u00e4 on tutkittu ja tutkitaan edelleen. T\u00e4ll\u00e4 hetkell\u00e4 t\u00e4rkeimm\u00e4t tutkimuskohteemme ovat i)\u00a0 Selvitt\u00e4\u00e4 ne virukset, jotka vaikuttavat vanhenemisprosessiin sin\u00e4ll\u00e4\u00e4n tai jotka voisivat olla patogeenisi\u00e4 juuri vanhuksille (keskittyen ns. endogeenisiin retroviruksiin, mutta my\u00f6s kaikki virukset, ns. viromi, analysoidaan) ii) Selvitt\u00e4\u00e4 ne molekyylit ja niiden toimintamekanismit, joiden tiedet\u00e4\u00e4n olevan nuoren ihmisen veriplasmassa ja jotka siirrettyn\u00e4 vanhuksiin vaikuttavat eri vanhenemismekanismien heikkenemiseen iii) Pitk\u00e4ik\u00e4isyyden genetiikkaa tutkitaan kansainv\u00e4listen meta-analyysien puitteissa.<\/span>\r\n\r\nTutkimuskohorttiimme kuuluvat ne Tervaskanto-tutkimukset, joista olemme ker\u00e4nneet biologiset n\u00e4ytteet, sek\u00e4 n\u00e4ytteet The Young Finns Study \u2013 kohortista. K\u00e4ytetyt metodit perustuvat DNA\/RNA NGS-sekvenointiin ja tulosten bioinformaattiseen analyysiin.<\/span>\r\n\r\nTutkimuksen t\u00e4m\u00e4nhetkiset rahoittajat<\/span>\r\n\r\nPirkanmaan sairaanhoitopiiri<\/span>\r\nSy\u00f6p\u00e4j\u00e4rjest\u00f6t<\/span>\r\nKulttuurirahasto<\/span>\r\nTampereen tuberkuloosis\u00e4\u00e4ti\u00f6<\/span>\r\n\r\nTutkimusryhm\u00e4<\/span>\r\nVastuullinen tutkija<\/span>\r\nProfessori Mikko Hurme, mikko.hurme@tuni.fi<\/a><\/span>\r\n\r\nTohtoriopiskelijat<\/span>\r\nTapio Nevalainen, tapio.nevalainen@tuni.fi<\/a><\/span>\r\nArttu Autio, arttu.autio@tuni.fi<\/a><\/span>\r\n\r\nKeskeiset julkaisut 2016-2019<\/span>\r\n\r\nKananen L, Marttila S, Nevalainen T, Kummola L, Junttila I, Mononen N, K\u00e4h\u00f6nen M, Raitakari OT, Hervonen A, Jylh\u00e4 M, Lehtim\u00e4ki T, Hurme M<\/strong>, Jylh\u00e4v\u00e4 J. The trajectory of the blood DNA methylome aging rate largely\u00a0 set before adulthood: evidence from two longitudinal studies. <\/span>AGE 38, 65, 2016.<\/span>\r\n\r\nKananen L, Marttila S, Nevalainen T, Jylh\u00e4v\u00e4 J, Mononen N, K\u00e4h\u00f6nen M, Raitakari OT, Lehtim\u00e4ki T, Hurme M<\/strong>. Aging-associated DNA methylation changes in middle-aged individuals: the Young Finns Study. <\/span>BMC Genomics 17, 103, 2016.<\/span>\r\n\r\n\u00a0Jylh\u00e4v\u00e4 J, Kananen L, Raitanen J, Marttila S, Nevalainen T, Hervonen A, Jylh\u00e4 M, Hurme M<\/strong>. Methylomic predictors demonstrate the role of NF-kB in old-age mortality and are unrelated to the aging-associated epigenetic drift. <\/span>Oncotarget 7, 19228, 2016.<\/span>\r\n\r\nCiccarone F, Malavolta M, Calabrese R, Guastafierro T,\u00a0 Bacalini NG, Reale A, Franceschi C, Capri M, Hervonen A, Hurme M<\/strong>, Grubeck-Loebenstein B, Koller B, Bernhardt J, Sch\u00f6n C, Slaagboom E, Touissant O, Sikora E, Gonos ES, Breusing N, Grune T, Jansen E, Dolle M, Moreno-Villanueva M, Sindlinger T, Burkle A, Zampieri M, Caiafa P.\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Age-dependent expression of DNMT1 and DNMT3B in PBMCs from a large European population enrolled in the MARK-AGE study. <\/span>Aging Cell 15, 755, 2016.<\/span>\r\n\r\nNevalainen T, Kananen L, Marttila S, Jylh\u00e4v\u00e4 J, Mononen N, K\u00e4h\u00f6nen M, Raitakari OT, Hervonen A, Jylh\u00e4 M, Lehtim\u00e4ki T, Hurme M<\/strong>. Obesity accelerates epigenetic aging in middle-aged but not in elderly individuals. <\/span>Clin Epigenetics 9, 20, 2017.<\/span>\r\n\r\nJoshi PK, Pirastu N, Kentistou KA, Fischer K, Hofer E, Schraut KE, Clark DW, Nutile T, Barnes CLK, Timmers PRHJ, Shen X, Gandin I, McDaid AF, Folkman Hansen T,\u00a0 Gordon SD, Giulianini F, Boutin TS, Abdelaoui A, Zhao W, Medina-Gomez C, Bartz TM, Trompet S, Lange LA, Raffield L, van der Spek A, Galesloot TE, Proitsi P, Yanek LR, Bielak LF, Payton A, Murgia F, Pina Concas M, Biino G, Tajuddin SM, Sepp\u00e4l\u00e4 I, Amin N, Boerwinkle E, Borglum AD, Campbell A, Demerath EW, Demuth I, Faul JD, Ford I, Gialluisi A, G\u00f6gele M, Graff M, Hingorani A, Hottenga J, Hougaard DM, Hurme M<\/strong>, Ikram MA, Jylh\u00e4 M, Kuh D, Ligthart L, Lill CM, Lindenberger U, Lumley T, M\u00e4gi T, Margues-Vidal P, Medland C, Milani L, Nagy R, Ollier WR, Peyser PA, Pramstaller PP, Ridker PM, Rivadeneira F, Ruggiero D, Saba Y, Schmidt R, Schmidt H, Slaagbom PE, Smith BH, Smith JA, Sotoodehnia N, Steinhagen-Thiessen\u00a0 E, van Rooij FJA, Verbeek AL, Vermeulen SH, Vollenweider P, Wang Y, Werge T, Whitfield JB, Zonderman AB, Lehtim\u00e4ki T, Evans MK, Pirastu M, Fuchsberger C, Bertram L, Pendleton N, Kardia SLR, Ciullo M, Becker DM, Wong A, Psaty BM,\u00a0 van Duijn CM, Franceschini, North KE, Weir DW, Metspalu A, Boomsma DI, Hayward C, Chasman D, Martin NG, Sattar N, Campbell H, Esko T, Kutalik Z, Wilson JF. Genome-wide meta-analysis associates HLA-DQA1\/DRB1 and LPA and lifestyle factors with human longevity.<\/span>\u00a0<\/strong>Nature Comm\u00a0 8, 610, 2017<\/span>\r\n\r\nNevalainen T, Autio A, Mishra B, Marttila S, Jylh\u00e4 M, Hurme M<\/strong>. Aging-associated patterns in the expression of human endogenous retroviruses. <\/strong><\/span>PLoS One 13, e0207407, 2018.<\/span>\r\n\r\nFiorito G, McCrory C, Robinson O, Carmeli C, Ochoa Rosales, C, Zhang Y, Colicino E, Dugue PA, Artaud F, McKay GJ, Jeong A, Mishra PP, Nost TH, Krogh V, Panico S, Sacerdote C, Tumino R, Palli D, Matullo G, Guarrera S, Gandini S, the BIOS Consortium, Bochud M, Dermitzakis E, Muka T, Schwartz J, Vokonas PS, Just A, Hodge AM, Giles GG, Southey MC, Hurme MA<\/strong>, Young I, McKnight AJ, Lund E, Baccarelli A, Milne R, Kenny RA, Elbaz A, Brenner H, Kee F, Voortman T, Probst-Hensch N, Lehtim\u00e4ki T, Elliot P, Stringhini S, Vineis P, Polodoro S, the Lifepath consortium. Socioeconomic position, lifestyle habits and biomarkers of epigenetic aging: a multi-cohort analysis. <\/span>Aging in press.<\/span>\r\n\r\nMandaviya PR, Joehanes R, Brody J, Castillo-Fernandez JE, Dekkers KKF, Do AN, Graff M, H\u00e4nninen IK, Tanaka T, de Jonge EAL, Kiefte-de Jong JC, Anbsher DM, Aslibekyan S, de Rijke YB, Fornage M, Herbandez DG, Hurme MA<\/strong>, Ikram MA, Jacques PF, Justice AE, Kiel DP, Lemaitre RN, Mendelson MM, Mikkil\u00e4 V, Moore AZ, Pallister T, Raitakari OT, Schalkwijk CG, Sha J, Slagboom EP, Smith CE, Stehower CDA, Tsai PC, Uitterlinden AG, van der Kallen CJH, van Heemst DD, BIOS consortium, CHARGE consortium, Arnett DK, Bandinelli S, Bell JT, Heijmans BBT, Lehtim\u00e4ki T, Levy D, North KE, Sotoodehnia N, van Greevenbroek MMJ, van Meurs JBJ, Heil SG. Association of dietary folate and vitamin B12 intake with genome-wide DNA methylation in blood: a large scale epigenome-wide analysis of 5,841 individuals. <\/span>Am J Clin Nutr in press<\/span>\r\n\r\nMeryk A, Pangrazzi L, Hagen M, Hatzmann F, Jenewein B, Jakic B, Hermann-Kleiter N, Baier G, Jylh\u00e4v\u00e4 J, Hurme M<\/strong>, Trieb K, Grubeck-Loebenstein B. Fcm receptor as a new costimulatory molecule for T cells. <\/span>Cell Rep in press<\/span>\r\n\r\nYhteisty\u00f6kumppanit<\/span>\r\n\r\nProfessori Marja Jylh\u00e4<\/span>\r\nProfessori Terho Lehtim\u00e4ki<\/span>[\/vc_column_text][\/vc_column][\/vc_row]","_fi_post_name":"immuunisysteemin-vanheneminen-solu-ja-molekyylitason-mekanismit-mikko-hurme","_fi_post_excerpt":"","_fi_post_title":"Immuunisysteemin vanheneminen: solu ja molekyylitason mekanismit \/ Mikko Hurme","_en_post_content":"[vc_row][vc_column][vc_column_text]Aging of the immune system: cellular and molecular mechanisms<\/span>\r\n\r\nThe function of the immune system in humans is severely compromised in elderly individuals leading to an increased frequency and severity of infectious diseases. In addition to this, it is associated with a low-degree inflammation, called inflammaging, which is in the background of several aging-associated phenotypic changes, e.g. frailty. During the last 5-7 years, we have characterized the aging-associated changes in the transcriptome, their functional consequences and possible regulatory factors. The focus has been in the epigenetics, i.e. mechanisms mediating the effect of environment and life-style factors on the activation of the genes. At present, the focus is on the following projects i) Viruses and immunosenescence. This far, only one virus, cytomegalovirus, is known to cause an exhaustion of the immune system. To analyze whether other viruses would have similar functions, the whole virome in the elderly individuals is characterized (using metagenomic and metatranscriptomic analyses) ii) Is there a \u201crejuvenating\u201d factor in the plasma of young individuals? Already several decades ago, the parabiosis approaches in animal models suggested that this would be the case ii) Genetics of longevity. This project (as well as the epigenetic epidemiology projects) are continued by participating in international meta-analyses.\r\n\r\nFor these projects, the Vitality 90+ cohorts where biological samples are available are used. The techniques required have already been used in our previous publications.\r\n\r\nResearch funding<\/span>\r\nPirkanmaa Hospital District\r\nCancer Society of Finland\r\nThe Finnish Cultural Foundation\r\nTampere Tuberculosis Foundation\r\n\r\nResearch group<\/span>\r\nPrincipal investigator\r\nProfessor Mikko Hurme, mikko.hurme@tuni.fi<\/a>\r\n\r\nDoctoral students\r\nTapio Nevalainen, tapio.nevalainen@tuni.fi<\/a>\r\nArttu Autio, arttu.autio@tuni.fi<\/a>\r\n\r\nSelected publications 2016\u20132019<\/span>\r\n\r\nKananen L, Marttila S, Nevalainen T, Kummola L, Junttila I, Mononen N, K\u00e4h\u00f6nen M, Raitakari OT, Hervonen A, Jylh\u00e4 M, Lehtim\u00e4ki T, Hurme M<\/strong>, Jylh\u00e4v\u00e4 J. The trajectory of the blood DNA methylome aging rate largely\u00a0 set before adulthood: evidence from two longitudinal studies. AGE 38, 65, 2016.\r\n\r\nKananen L, Marttila S, Nevalainen T, Jylh\u00e4v\u00e4 J, Mononen N, K\u00e4h\u00f6nen M, Raitakari OT, Lehtim\u00e4ki T, Hurme M<\/strong>. Aging-associated DNA methylation changes in middle-aged individuals: the Young Finns Study. BMC Genomics 17, 103, 2016.\r\n\r\nJylh\u00e4v\u00e4 J, Kananen L, Raitanen J, Marttila S, Nevalainen T, Hervonen A, Jylh\u00e4 M, Hurme M<\/strong>. Methylomic predictors demonstrate the role of NF-kB in old-age mortality and are unrelated to the aging-associated epigenetic drift. Oncotarget 7, 19228, 2016.\r\n\r\nCiccarone F, Malavolta M, Calabrese R, Guastafierro T,\u00a0 Bacalini NG, Reale A, Franceschi C, Capri M, Hervonen A, Hurme M<\/strong>, Grubeck-Loebenstein B, Koller B, Bernhardt J, Sch\u00f6n C, Slaagboom E, Touissant O, Sikora E, Gonos ES, Breusing N, Grune T, Jansen E, Dolle M, Moreno-Villanueva M, Sindlinger T, Burkle A, Zampieri M, Caiafa P. Age-dependent expression of DNMT1 and DNMT3B in PBMCs from a large European population enrolled in the MARK-AGE study. Aging Cell 15, 755, 2016.\r\n\r\nNevalainen T, Kananen L, Marttila S, Jylh\u00e4v\u00e4 J, Mononen N, K\u00e4h\u00f6nen M, Raitakari OT, Hervonen A, Jylh\u00e4 M, Lehtim\u00e4ki T, Hurme M<\/strong>. Obesity accelerates epigenetic aging in middle-aged but not in elderly individuals. Clin Epigenetics 9, 20, 2017.\r\n\r\nJoshi PK, Pirastu N, Kentistou KA, Fischer K, Hofer E, Schraut KE, Clark DW, Nutile T, Barnes CLK, Timmers PRHJ, Shen X, Gandin I, McDaid AF, Folkman Hansen T,\u00a0 Gordon SD, Giulianini F, Boutin TS, Abdelaoui A, Zhao W, Medina-Gomez C, Bartz TM, Trompet S, Lange LA, Raffield L, van der Spek A, Galesloot TE, Proitsi P, Yanek LR, Bielak LF, Payton A, Murgia F, Pina Concas M, Biino G, Tajuddin SM, Sepp\u00e4l\u00e4 I, Amin N, Boerwinkle E, Borglum AD, Campbell A, Demerath EW, Demuth I, Faul JD, Ford I, Gialluisi A, G\u00f6gele M, Graff M, Hingorani A, Hottenga J, Hougaard DM, Hurme M<\/strong>, Ikram MA, Jylh\u00e4 M, Kuh D, Ligthart L, Lill CM, Lindenberger U, Lumley T, M\u00e4gi T, Margues-Vidal P, Medland C, Milani L, Nagy R, Ollier WR, Peyser PA, Pramstaller PP, Ridker PM, Rivadeneira F, Ruggiero D, Saba Y, Schmidt R, Schmidt H, Slaagbom PE, Smith BH, Smith JA, Sotoodehnia N, Steinhagen-Thiessen\u00a0 E, van Rooij FJA, Verbeek AL, Vermeulen SH, Vollenweider P, Wang Y, Werge T, Whitfield JB, Zonderman AB, Lehtim\u00e4ki T, Evans MK, Pirastu M, Fuchsberger C, Bertram L, Pendleton N, Kardia SLR, Ciullo M, Becker DM, Wong A, Psaty BM,\u00a0 van Duijn CM, Franceschini, North KE, Weir DW, Metspalu A, Boomsma DI, Hayward C, Chasman D, Martin NG, Sattar N, Campbell H, Esko T, Kutalik Z, Wilson JF. Genome-wide meta-analysis associates HLA-DQA1\/DRB1 and LPA and lifestyle factors with human longevity.\u00a0<\/strong>Nature Comm\u00a0 8, 610, 2017\r\n\r\nNevalainen T, Autio A, Mishra B, Marttila S, Jylh\u00e4 M, Hurme M<\/strong>. Aging-associated patterns in the expression of human endogenous retroviruses. <\/strong>PLoS One 13, e0207407, 2018.\r\n\r\nFiorito G, McCrory C, Robinson O, Carmeli C, Ochoa Rosales, C, Zhang Y, Colicino E, Dugue PA, Artaud F, McKay GJ, Jeong A, Mishra PP, Nost TH, Krogh V, Panico S, Sacerdote C, Tumino R, Palli D, Matullo G, Guarrera S, Gandini S, the BIOS Consortium, Bochud M, Dermitzakis E, Muka T, Schwartz J, Vokonas PS, Just A, Hodge AM, Giles GG, Southey MC, Hurme MA<\/strong>, Young I, McKnight AJ, Lund E, Baccarelli A, Milne R, Kenny RA, Elbaz A, Brenner H, Kee F, Voortman T, Probst-Hensch N, Lehtim\u00e4ki T, Elliot P, Stringhini S, Vineis P, Polodoro S, the Lifepath consortium. Socioeconomic position, lifestyle habits and biomarkers of epigenetic aging: a multi-cohort analysis. Aging in press.\r\n\r\nMandaviya PR, Joehanes R, Brody J, Castillo-Fernandez JE, Dekkers KKF, Do AN, Graff M, H\u00e4nninen IK, Tanaka T, de Jonge EAL, Kiefte-de Jong JC, Anbsher DM, Aslibekyan S, de Rijke YB, Fornage M, Herbandez DG, Hurme MA<\/strong>, Ikram MA, Jacques PF, Justice AE, Kiel DP, Lemaitre RN, Mendelson MM, Mikkil\u00e4 V, Moore AZ, Pallister T, Raitakari OT, Schalkwijk CG, Sha J, Slagboom EP, Smith CE, Stehower CDA, Tsai PC, Uitterlinden AG, van der Kallen CJH, van Heemst DD, BIOS consortium, CHARGE consortium, Arnett DK, Bandinelli S, Bell JT, Heijmans BBT, Lehtim\u00e4ki T, Levy D, North KE, Sotoodehnia N, van Greevenbroek MMJ, van Meurs JBJ, Heil SG. Association of dietary folate and vitamin B12 intake with genome-wide DNA methylation in blood: a large scale epigenome-wide analysis of 5,841 individuals. Am J Clin Nutr in press\r\n\r\nMeryk A, Pangrazzi L, Hagen M, Hatzmann F, Jenewein B, Jakic B, Hermann-Kleiter N, Baier G, Jylh\u00e4v\u00e4 J, Hurme M<\/strong>, Trieb K, Grubeck-Loebenstein B. Fcm receptor as a new costimulatory molecule for T cells. Cell Rep in press\r\n\r\nCollaborators<\/span>\r\nProfessor Marja Jylh\u00e4\r\nProfessor Terho Lehtim\u00e4ki[\/vc_column_text][\/vc_column][\/vc_row]","_en_post_name":"aging-of-the-immune-system","_en_post_excerpt":"","_en_post_title":"Aging of the immune system: cellular and molecular mechanisms \/ Mikko Hurme","edit_language":"en","footnotes":""},"class_list":["post-5688","page","type-page","status-publish","hentry","entry","no-media"],"_links":{"self":[{"href":"https:\/\/www.gerec.fi\/en\/wp-json\/wp\/v2\/pages\/5688","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.gerec.fi\/en\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.gerec.fi\/en\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.gerec.fi\/en\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.gerec.fi\/en\/wp-json\/wp\/v2\/comments?post=5688"}],"version-history":[{"count":10,"href":"https:\/\/www.gerec.fi\/en\/wp-json\/wp\/v2\/pages\/5688\/revisions"}],"predecessor-version":[{"id":6577,"href":"https:\/\/www.gerec.fi\/en\/wp-json\/wp\/v2\/pages\/5688\/revisions\/6577"}],"up":[{"embeddable":true,"href":"https:\/\/www.gerec.fi\/en\/wp-json\/wp\/v2\/pages\/5661"}],"wp:attachment":[{"href":"https:\/\/www.gerec.fi\/en\/wp-json\/wp\/v2\/media?parent=5688"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}