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[{"key": "dc.contributor.advisor", "value": "Sillanp\u00e4\u00e4, Elina", "language": "", "element": "contributor", "qualifier": "advisor", "schema": "dc"}, {"key": "dc.contributor.advisor", "value": "F\u00f6hr, Tiina", "language": "", "element": "contributor", "qualifier": "advisor", "schema": "dc"}, {"key": "dc.contributor.author", "value": "Sanchez, Riikka", "language": "", "element": "contributor", "qualifier": "author", "schema": "dc"}, {"key": "dc.date.accessioned", "value": "2021-07-02T07:23:56Z", "language": null, "element": "date", "qualifier": "accessioned", "schema": "dc"}, {"key": "dc.date.available", "value": "2021-07-02T07:23:56Z", "language": null, "element": "date", "qualifier": "available", "schema": "dc"}, {"key": "dc.date.issued", "value": "2021", "language": "", "element": "date", "qualifier": "issued", "schema": "dc"}, {"key": "dc.identifier.uri", "value": "https://jyx.jyu.fi/handle/123456789/76959", "language": null, "element": "identifier", "qualifier": "uri", "schema": "dc"}, {"key": "dc.description.abstract", "value": "Biologista ik\u00e4\u00e4 voidaan arvioida monilla erilaisilla mittareilla. Toistaiseksi lupaavin biologinen ik\u00e4ennuste saadaan epigeneettist\u00e4 kelloa k\u00e4ytt\u00e4en. Epigeneettiset kellot perustuvat DNA:n metyloitumiseen. Kronologista ik\u00e4\u00e4 korkeamman epigeneettisen i\u00e4n on havaittu lis\u00e4\u00e4v\u00e4n ennenaikaisen kuo-leman riski\u00e4, mutta yhteyden voimakkuudesta on erilaisia arvioita. Epigeneettinen ik\u00e4\u00e4ntymisnopeus kuvaa eroa kronologisen i\u00e4n ja epigeneettisen i\u00e4n v\u00e4lill\u00e4. T\u00e4m\u00e4n tutkielman tarkoituksena oli selvitt\u00e4\u00e4, ennustaako uuden sukupolven GrimAge- epigeneettisen kellon avulla m\u00e4\u00e4ritetty epigeneettinen ik\u00e4\u00e4ntymisnopeus kuolleisuutta ja onko epigeneettisell\u00e4 i\u00e4ll\u00e4 yhteytt\u00e4 kuolleisuuteen, kun perim\u00e4 ja lapsuusajan ymp\u00e4rist\u00f6tekij\u00e4t kontrolloidaan kokonaan tai osittain kaksosmallinnuksen avulla. Lis\u00e4ksi tarkasteltiin selitt\u00e4v\u00e4tk\u00f6 tutkittavien tupakointi, painoindeksi tai fyysinen aktiivisuus mahdollista kaksosparien v\u00e4list\u00e4 eroa epigeneettisess\u00e4 i\u00e4ss\u00e4. \n\nTutkielmassa k\u00e4ytettiin Suomen kaksoskohortin alaotosta. Aineisto koostui 413 naisesta, jotka olivat 63\u201376-vuotiaita seurannan alussa. Epigeneettisen ik\u00e4\u00e4ntymisnopeuden ja kuolleisuusriskin yhteytt\u00e4 tarkasteltiin mallintamalla elossaoloaikoja k\u00e4ytt\u00e4en Cox regressioanalyysi\u00e4. Kaplanin-Meierin menetelm\u00e4ll\u00e4 ja log-rank-testill\u00e4 arvioitiin kuoleman todenn\u00e4k\u00f6isyyksi\u00e4 seuranta-aikana. T\u00e4ss\u00e4 analyysissa kaksosia k\u00e4siteltiin toisistaan riippumattomina yksil\u00f6in\u00e4. Epigeneettisesti vanhemman kaksosen todenn\u00e4k\u00f6isyytt\u00e4 kuolla ennen sisartaan arvioitiin kahden riippuvan otoksen McNemar-testill\u00e4. Riippuvan otoksen t-testill\u00e4 arvioitiin selitt\u00e4v\u00e4tk\u00f6 elintavat epigeneettisen ik\u00e4\u00e4ntymisnopeuden eroa kaksosten v\u00e4lill\u00e4.\n\nSeuranta-aikana (ka 15,8 [0,2\u201318,3] vuotta) kuoli yhteens\u00e4 156 tutkittavaa. Korkeampi epigeneettinen ik\u00e4\u00e4ntymisnopeus oli yhteydess\u00e4 kohonneeseen kuolleisuusriskiin. Epigeneettisen ik\u00e4\u00e4ntymisnopeuden kasvaessa yhden keskihajonnan (kh 3,19) verran kasvoi kuoleman riski 28 % (95 %:n luot-tamusv\u00e4li 11\u201347 %). Eri terveys- ja elintapamuuttujien sek\u00e4 koulutuksen vakioimisen vaikutus oli melko v\u00e4h\u00e4inen; kaikissa malleissa kuoleman riski kasvoi noin 24\u201331 % ik\u00e4\u00e4ntymisnopeuden kasvaessa yhden keskihajonnan verran. Kaplan-Meier-kuvaajien vertailussa epigeneettisen ik\u00e4\u00e4ntymisnopeuden tertiileist\u00e4 \u201dhitaasti ik\u00e4\u00e4ntyv\u00e4t\u201d erosivat tilastollisesti merkitsev\u00e4sti nopeasti ik\u00e4\u00e4ntyvist\u00e4 (p = 0,024), mutta \u201dkeskim\u00e4\u00e4r\u00e4isesti ik\u00e4\u00e4ntyv\u00e4t\u201d eiv\u00e4t eronneet \u201dhitaasti ik\u00e4\u00e4ntyvist\u00e4\u201d tai \u201dnopeasti ik\u00e4\u00e4ntyvist\u00e4\u201d (p = 0,450, p = 0,143). Epigeneettisen ik\u00e4\u00e4ntymisnopeuden ja kaksossisarten keskin\u00e4isen kuolinj\u00e4rjestyksen v\u00e4lill\u00e4 ei havaittu tilastollisesti merkitsev\u00e4\u00e4 yhteytt\u00e4. Ik\u00e4\u00e4ntymisnopeuden suhteen erilaisten kaksosten hitaammin ik\u00e4\u00e4ntyvill\u00e4 kaksosilla tupakoinnin askivuosien keskiarvo (1,59, kh 6,87) osoittautui tilastollisesti merkitsev\u00e4sti pienemm\u00e4ksi kuin nopeammin ik\u00e4\u00e4ntyvien keskiarvo (7,20, kh 13,48, ryhmien v\u00e4linen ero p < 0,001). \n\nTutkimustulokset vahvistavat aiempien tutkimusten havaintoja epigeneettisen ik\u00e4\u00e4ntymisnopeuden ja kuolleisuuden v\u00e4lisest\u00e4 yhteydest\u00e4. Tulokset my\u00f6s osoittavat, ett\u00e4 perinn\u00f6llisten tekij\u00f6iden lis\u00e4ksi elintapatekij\u00e4t vaikuttavat epigeneettiseen ik\u00e4\u00e4ntymiseen ja ett\u00e4 niill\u00e4 on t\u00e4rke\u00e4 rooli epigeneettisen ik\u00e4\u00e4ntymisen ja kuolleisuuden v\u00e4lisess\u00e4 yhteydess\u00e4. Lis\u00e4tutkimusta kuitenkin tarvitaan sen selvitt\u00e4miseksi, ovatko DNA:n metyloitumisessa tapahtuvat muutokset ik\u00e4\u00e4ntymisen syy vai seuraus.", "language": "fi", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.abstract", "value": "The most promising new biological age predictor is the epigenetic clock. Epigenetic clocks are based on DNA methylation. Higher epigenetic age compared to chronological age has been found to increase the risk of premature death, but the strength of the association has varied in different studies. Epigenetic age acceleration describes the difference between chronological age and epigenetic age. The purpose of this study was to investigate the association of epigenetic age acceleration with mortality and if epigenetic age acceleration is associated with mortality when genetic and childhood environmental factors are fully or partially controlled. In addition, it was examined whether smoking, body mass index or physical activity explains the possible epigenetic age difference within twin pairs. \n\nThe study sample is a sub-sample of the Finnish twin cohort. The sample consisted of 413 women aged 63\u201376 years at the beginning of the mortality follow-up. The association between epigenetic age acceleration and mortality risk was examined by modeling survival times using Cox regression analysis. Epigenetic age was determined by the second-generation epigenetic clock GrimAge. The Kaplan-Meier method and log-rank test were used to evaluate the probabilities of death during the follow-up. Mortality analyses were conducted for individuals. The probability of an epigenetically older twin dying first was assessed by McNemar test. The dependent t-test for paired samples was used to determine whether the lifestyle variables explained the difference in epigenetic age acceleration within twin pairs.\n\n156 participants died during the follow-up period (average 15,8 [0,2\u201318,3] years). A higher epigenetic age acceleration was associated with an increased risk of mortality. More precisely when the epigenetic age acceleration increased by one standard deviation (SD 3,19), the risk of death increased by 28% (95 % Cl 11\u201347%). The impact of the adjustment for various health and lifestyle variables as well as education was rather small. In all models, the risk of death increased by about 24\u201331% per one SD increase in the age acceleration. Comparing survival between epigenetic age acceleration tertiles showed that \u201cslow agers\u201d differed statistically significantly from \u201cfast agers\u201d (p = 0,024), but the \u201cmedium agers\u201d did not differ from \u201cslow agers\u201d (p = 0,450) or \u201cfast agers\u201d (p = 0,143). No statistically significant association was found between the epigenetic age acceleration and the twin death order. Epigenetically younger twins had statistically significantly lower average number of smoking pack-years (1,59, SD 6,87) when compared to their faster aging twin siblings (7,20, SD 13,48, difference between groups p < 0,001).\n\nThe results support findings from previous studies on the association between epigenetic age acceleration and mortality. The results also show that lifestyle factors contribute to epigenetic aging and play an important role in the association between epigenetic aging and mortality. However, further research is needed to determine whether changes in DNA methylation are a cause or a consequence of aging.", "language": "en", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Submitted by Miia Hakanen (mihakane@jyu.fi) on 2021-07-02T07:23:56Z\nNo. of bitstreams: 0", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Made available in DSpace on 2021-07-02T07:23:56Z (GMT). No. of bitstreams: 0\n Previous issue date: 2021", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.format.extent", "value": "65", "language": "", "element": "format", "qualifier": "extent", "schema": "dc"}, {"key": "dc.format.mimetype", "value": "application/pdf", "language": null, "element": "format", "qualifier": "mimetype", "schema": "dc"}, {"key": "dc.language.iso", "value": "fin", "language": null, "element": "language", "qualifier": "iso", "schema": "dc"}, {"key": "dc.rights", "value": "In Copyright", "language": "en", "element": "rights", "qualifier": null, "schema": "dc"}, {"key": "dc.subject.other", "value": "biologinen ik\u00e4\u00e4ntyminen", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "epigeneettinen ik\u00e4\u00e4ntymisnopeus", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "epigeneettinen kello", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "GrimAge", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.title", "value": "Epigeneettisen ik\u00e4\u00e4ntymisnopeuden yhteys kuolleisuuteen", "language": "", "element": "title", "qualifier": null, "schema": "dc"}, {"key": "dc.type", "value": "master thesis", "language": null, "element": "type", "qualifier": null, "schema": "dc"}, {"key": "dc.identifier.urn", "value": "URN:NBN:fi:jyu-202107024146", "language": "", "element": "identifier", "qualifier": "urn", "schema": "dc"}, {"key": "dc.type.ontasot", "value": "Pro gradu -tutkielma", "language": "fi", "element": "type", "qualifier": "ontasot", "schema": "dc"}, {"key": "dc.type.ontasot", "value": "Master\u2019s thesis", "language": "en", "element": "type", "qualifier": "ontasot", "schema": "dc"}, {"key": "dc.contributor.faculty", "value": "Liikuntatieteellinen tiedekunta", "language": "fi", "element": "contributor", "qualifier": "faculty", "schema": "dc"}, {"key": "dc.contributor.faculty", "value": "Faculty of Sport and Health Sciences", "language": "en", "element": "contributor", "qualifier": "faculty", "schema": "dc"}, {"key": "dc.contributor.department", "value": "Liikunta- ja terveystieteet", "language": "fi", "element": "contributor", "qualifier": "department", "schema": "dc"}, {"key": "dc.contributor.department", "value": "Sport and Health Sciences", "language": "en", "element": "contributor", "qualifier": "department", "schema": "dc"}, {"key": "dc.contributor.organization", "value": "Jyv\u00e4skyl\u00e4n yliopisto", "language": "fi", "element": "contributor", "qualifier": "organization", "schema": "dc"}, {"key": "dc.contributor.organization", "value": "University of Jyv\u00e4skyl\u00e4", "language": "en", "element": "contributor", "qualifier": "organization", "schema": "dc"}, {"key": "dc.subject.discipline", "value": "Gerontologia ja kansanterveys", "language": "fi", "element": "subject", "qualifier": "discipline", "schema": "dc"}, {"key": "dc.subject.discipline", "value": "Gerontology and Public Health", "language": "en", "element": "subject", "qualifier": "discipline", "schema": "dc"}, {"key": "yvv.contractresearch.funding", "value": "0", "language": "", "element": "contractresearch", "qualifier": "funding", "schema": "yvv"}, {"key": "dc.type.coar", "value": "http://purl.org/coar/resource_type/c_bdcc", "language": null, "element": "type", "qualifier": "coar", "schema": "dc"}, {"key": "dc.rights.accesslevel", "value": "openAccess", "language": null, "element": "rights", "qualifier": "accesslevel", "schema": "dc"}, {"key": "dc.type.publication", "value": "masterThesis", "language": null, "element": "type", "qualifier": "publication", "schema": "dc"}, {"key": "dc.subject.oppiainekoodi", "value": "50423", "language": "", "element": "subject", "qualifier": "oppiainekoodi", "schema": "dc"}, {"key": "dc.subject.yso", "value": "elintavat", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "ik\u00e4\u00e4ntyminen", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "epigenetiikka", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "kuolleisuus", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.format.content", "value": "fulltext", "language": null, "element": "format", "qualifier": "content", "schema": "dc"}, {"key": "dc.rights.url", "value": "https://rightsstatements.org/page/InC/1.0/", "language": null, "element": "rights", "qualifier": "url", "schema": "dc"}, {"key": "dc.type.okm", "value": "G2", "language": null, "element": "type", "qualifier": "okm", "schema": "dc"}]
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