{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T20:38:41Z","timestamp":1793997521557,"version":"4.8.0"},"reference-count":63,"publisher":"National Academy of Sciences","issue":"23","license":[{"start":{"date-parts":[[2019,5,21]],"date-time":"2019-05-21T00:00:00Z","timestamp":1558396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2019,6,4]]},"abstract":"<jats:p>\n                    Aging and psychosocial stress are associated with increased inflammation and disease risk, but the underlying molecular mechanisms are unclear. Because both aging and stress are also associated with lasting epigenetic changes, a plausible hypothesis is that stress along the lifespan could confer disease risk through epigenetic effects on molecules involved in inflammatory processes. Here, by combining large-scale analyses in human cohorts with experiments in cells, we report that FKBP5, a protein implicated in stress physiology, contributes to these relations. Across independent human cohorts (total\n                    <jats:italic>n<\/jats:italic>\n                    &gt; 3,000), aging synergized with stress-related phenotypes, measured with childhood trauma and major depression questionnaires, to epigenetically up-regulate\n                    <jats:italic>FKBP5<\/jats:italic>\n                    expression. These age\/stress-related epigenetic effects were recapitulated in a cellular model of replicative senescence, whereby we exposed replicating human fibroblasts to stress (glucocorticoid) hormones. Unbiased genome-wide analyses in human blood linked higher\n                    <jats:italic>FKBP5<\/jats:italic>\n                    mRNA with a proinflammatory profile and altered NF-\u03baB\u2013related gene networks. Accordingly, experiments in immune cells showed that higher\n                    <jats:italic>FKBP5<\/jats:italic>\n                    promotes inflammation by strengthening the interactions of NF-\u03baB regulatory kinases, whereas opposing FKBP5 either by genetic deletion (CRISPR\/Cas9-mediated) or selective pharmacological inhibition prevented the effects on NF-\u03baB. Further, the age\/stress-related epigenetic signature enhanced\n                    <jats:italic>FKBP5<\/jats:italic>\n                    response to NF-\u03baB through a positive feedback loop and was present in individuals with a history of acute myocardial infarction, a disease state linked to peripheral inflammation. These findings suggest that aging\/stress-driven FKBP5\u2013NF-\u03baB signaling mediates inflammation, potentially contributing to cardiovascular risk, and may thus point to novel biomarker and treatment possibilities.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1816847116","type":"journal-article","created":{"date-parts":[[2019,5,21]],"date-time":"2019-05-21T18:00:10Z","timestamp":1558461610000},"page":"11370-11379","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":366,"title":["Epigenetic upregulation of FKBP5 by aging and stress contributes to NF-\u03baB\u2013driven inflammation and cardiovascular risk"],"prefix":"10.1073","volume":"116","author":[{"given":"Anthony S.","family":"Zannas","sequence":"first","affiliation":[{"name":"Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, 80804 Munich, Germany;"},{"name":"Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514;"},{"name":"Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514;"},{"name":"Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiwen","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, 80804 Munich, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Hafner","sequence":"additional","affiliation":[{"name":"Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, 80804 Munich, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Baumert","sequence":"additional","affiliation":[{"name":"Institute of Epidemiology, Helmholtz Zentrum M\u00fcnchen - German Research Centre for Environmental Health, D-85764 Neuherberg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Wiechmann","sequence":"additional","affiliation":[{"name":"Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, 80804 Munich, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julius C.","family":"Pape","sequence":"additional","affiliation":[{"name":"Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, 80804 Munich, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janine","family":"Arloth","sequence":"additional","affiliation":[{"name":"Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, 80804 Munich, Germany;"},{"name":"Institute of Computational Biology, Helmholtz Zentrum M\u00fcnchen, D-85764 Neuherberg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maik","family":"K\u00f6del","sequence":"additional","affiliation":[{"name":"Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, 80804 Munich, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Martinelli","sequence":"additional","affiliation":[{"name":"Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, 80804 Munich, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Roitman","sequence":"additional","affiliation":[{"name":"Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, 80804 Munich, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7450-0871","authenticated-orcid":false,"given":"Simone","family":"R\u00f6h","sequence":"additional","affiliation":[{"name":"Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, 80804 Munich, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Haehle","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Institute of Organic Chemistry and Biochemistry, Technische Universit\u00e4t Darmstadt, 64289 Darmstadt, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca T.","family":"Emeny","sequence":"additional","affiliation":[{"name":"Geisel School of Medicine, Dartmouth College, Lebanon, NH 03755;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stella","family":"Iurato","sequence":"additional","affiliation":[{"name":"Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, 80804 Munich, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"Carrillo-Roa","sequence":"additional","affiliation":[{"name":"Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, 80804 Munich, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jari","family":"Lahti","sequence":"additional","affiliation":[{"name":"Department of Psychology and Logopedics, University of Helsinki, 00100 Helsinki, Finland;"},{"name":"Turku Institute for Advanced Studies, University of Turku, 20500 Turku, Finland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katri","family":"R\u00e4ikk\u00f6nen","sequence":"additional","affiliation":[{"name":"Department of Psychology and Logopedics, University of Helsinki, 00100 Helsinki, Finland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan G.","family":"Eriksson","sequence":"additional","affiliation":[{"name":"Department of General Practice and Primary Health Care, Helsinki University Hospital, University of Helsinki, 00100 Helsinki, Finland;"},{"name":"Folkh\u00e4lsan Research Center, 00290 Helsinki, Finland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda J.","family":"Drake","sequence":"additional","affiliation":[{"name":"University\/British Heart Foundation Centre for Cardiovascular Science, The Queen\u2019s Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Waldenberger","sequence":"additional","affiliation":[{"name":"Institute of Epidemiology, Helmholtz Zentrum M\u00fcnchen - German Research Centre for Environmental Health, D-85764 Neuherberg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Wahl","sequence":"additional","affiliation":[{"name":"Institute of Epidemiology, Helmholtz Zentrum M\u00fcnchen - German Research Centre for Environmental Health, D-85764 Neuherberg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Kunze","sequence":"additional","affiliation":[{"name":"Institute of Epidemiology, Helmholtz Zentrum M\u00fcnchen - German Research Centre for Environmental Health, D-85764 Neuherberg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Lucae","sequence":"additional","affiliation":[{"name":"Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, 80804 Munich, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bekh","family":"Bradley","sequence":"additional","affiliation":[{"name":"Atlanta Veterans Affairs Medical Center, Decatur, GA 30033;"},{"name":"Department of Psychiatry and Behavioral Sciences, Emory University Medical School, Atlanta, GA 30322;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Gieger","sequence":"additional","affiliation":[{"name":"Institute of Epidemiology, Helmholtz Zentrum M\u00fcnchen - German Research Centre for Environmental Health, D-85764 Neuherberg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Hausch","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Institute of Organic Chemistry and Biochemistry, Technische Universit\u00e4t Darmstadt, 64289 Darmstadt, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8537-5156","authenticated-orcid":false,"given":"Alicia K.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Emory University Medical School, Atlanta, GA 30322;"},{"name":"Department of Gynecology and Obstetrics, Emory University Medical School, Atlanta, GA 30322;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerry J.","family":"Ressler","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Emory University Medical School, Atlanta, GA 30322;"},{"name":"Division of Depression &amp; Anxiety Disorders, McLean Hospital, Belmont, MA 02478;"},{"name":"Department of Psychiatry, Harvard Medical School, Boston, MA 02478;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertram","family":"M\u00fcller-Myhsok","sequence":"additional","affiliation":[{"name":"Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, 80804 Munich, Germany;"},{"name":"Munich Cluster of Systems Biology, SyNergy, 80539 Munich, Germany;"},{"name":"Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl-Heinz","family":"Ladwig","sequence":"additional","affiliation":[{"name":"Institute of Epidemiology, Helmholtz Zentrum M\u00fcnchen - German Research Centre for Environmental Health, D-85764 Neuherberg, Germany;"},{"name":"Department of Psychosomatic Medicine and Psychotherapy, Klinikum rechts der Isar, Technische Universit\u00e4t M\u00fcnchen, 80333 M\u00fcnchen, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theo","family":"Rein","sequence":"additional","affiliation":[{"name":"Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, 80804 Munich, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils C.","family":"Gassen","sequence":"additional","affiliation":[{"name":"Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, 80804 Munich, Germany;"},{"name":"Department of Psychiatry and Psychotherapy, University Hospital Bonn, 53105 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth B.","family":"Binder","sequence":"additional","affiliation":[{"name":"Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, 80804 Munich, Germany;"},{"name":"Department of Psychiatry and Behavioral Sciences, Emory University Medical School, Atlanta, GA 30322;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2019,5,21]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"R741","DOI":"10.1016\/j.cub.2012.07.024","article-title":"Ageing as a risk factor for disease","volume":"22","author":"Niccoli T.","year":"2012","unstructured":"T. Niccoli, L. Partridge, Ageing as a risk factor for disease. Curr. Biol. 22, R741\u2013R752 (2012).","journal-title":"Curr. Biol."},{"key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.yjmcc.2014.12.006","article-title":"Programming of cardiovascular disease across the life-course","volume":"83","author":"Blackmore H. L.","year":"2015","unstructured":"H. L. Blackmore, S. E. Ozanne, Programming of cardiovascular disease across the life-course. J. Mol. Cell Cardiol. 83, 122\u2013130 (2015).","journal-title":"J. Mol. Cell Cardiol."},{"key":"e_1_3_4_3_2","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.physbeh.2011.08.019","article-title":"Adverse childhood experiences, allostasis, allostatic load, and age-related disease","volume":"106","author":"Danese A.","year":"2012","unstructured":"A. Danese, B. S. McEwen, Adverse childhood experiences, allostasis, allostatic load, and age-related disease. Physiol. Behav. 106, 29\u201339 (2012).","journal-title":"Physiol. Behav."},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/S0749-3797(98)00017-8","article-title":"Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. The Adverse Childhood Experiences (ACE) study","volume":"14","author":"Felitti V. J.","year":"1998","unstructured":"V. J. Felitti ., Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. The Adverse Childhood Experiences (ACE) study. Am. J. Prev. Med. 14, 245\u2013258 (1998).","journal-title":"Am. J. Prev. Med."},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1001\/archpsyc.65.4.409","article-title":"Elevated inflammation levels in depressed adults with a history of childhood maltreatment","volume":"65","author":"Danese A.","year":"2008","unstructured":"A. Danese ., Elevated inflammation levels in depressed adults with a history of childhood maltreatment. Arch. Gen. Psychiatry 65, 409\u2013415 (2008).","journal-title":"Arch. Gen. Psychiatry"},{"key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1001\/jama.290.2.215","article-title":"Depressive symptoms and health-related quality of life: The heart and soul study","volume":"290","author":"Ruo B.","year":"2003","unstructured":"B. Ruo ., Depressive symptoms and health-related quality of life: The heart and soul study. JAMA 290, 215\u2013221 (2003).","journal-title":"JAMA"},{"key":"e_1_3_4_7_2","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s11886-017-0919-x","article-title":"Psychological stress, inflammation, and coronary heart disease","volume":"19","author":"Wirtz P. H.","year":"2017","unstructured":"P. H. Wirtz, R. von K\u00e4nel, Psychological stress, inflammation, and coronary heart disease. Curr. Cardiol. Rep. 19, 111 (2017).","journal-title":"Curr. Cardiol. Rep."},{"key":"e_1_3_4_8_2","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1073\/pnas.0610362104","article-title":"Childhood maltreatment predicts adult inflammation in a life-course study","volume":"104","author":"Danese A.","year":"2007","unstructured":"A. Danese, C. M. Pariante, A. Caspi, A. Taylor, R. Poulton, Childhood maltreatment predicts adult inflammation in a life-course study. Proc. Natl. Acad. Sci. U.S.A. 104, 1319\u20131324 (2007).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"e_1_3_4_9_2","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1017\/S0033291706007574","article-title":"Depressive symptoms and C-reactive protein: The cardiovascular risk in Young Finns study","volume":"36","author":"Elovainio M.","year":"2006","unstructured":"M. Elovainio .; Cardiovascular Risk in Young Finns Study, Depressive symptoms and C-reactive protein: The cardiovascular risk in Young Finns study. Psychol. Med. 36, 797\u2013805 (2006).","journal-title":"Psychol. Med."},{"key":"e_1_3_4_10_2","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1001\/archpediatrics.2009.214","article-title":"Adverse childhood experiences and adult risk factors for age-related disease: Depression, inflammation, and clustering of metabolic risk markers","volume":"163","author":"Danese A.","year":"2009","unstructured":"A. Danese ., Adverse childhood experiences and adult risk factors for age-related disease: Depression, inflammation, and clustering of metabolic risk markers. Arch. Pediatr. Adolesc. Med. 163, 1135\u20131143 (2009).","journal-title":"Arch. Pediatr. Adolesc. Med."},{"key":"e_1_3_4_11_2","doi-asserted-by":"crossref","first-page":"2537","DOI":"10.1093\/eurheartj\/ehi456","article-title":"C-reactive protein, depressed mood, and the prediction of coronary heart disease in initially healthy men: Results from the MONICA-KORA Augsburg Cohort study 1984-1998","volume":"26","author":"Ladwig K. H.","year":"2005","unstructured":"K. H. Ladwig, B. Marten-Mittag, H. L\u00f6wel, A. D\u00f6ring, W. Koenig; MONICA-KORA Augsburg Cohort Study 1984-1998, C-reactive protein, depressed mood, and the prediction of coronary heart disease in initially healthy men: Results from the MONICA-KORA Augsburg Cohort study 1984-1998. Eur. Heart J. 26, 2537\u20132542 (2005).","journal-title":"Eur. Heart J."},{"key":"e_1_3_4_12_2","doi-asserted-by":"crossref","first-page":"4395","DOI":"10.1128\/MCB.15.8.4395","article-title":"FKBP51, a novel T-cell-specific immunophilin capable of calcineurin inhibition","volume":"15","author":"Baughman G.","year":"1995","unstructured":"G. Baughman, G. J. Wiederrecht, N. F. Campbell, M. M. Martin, S. Bourgeois, FKBP51, a novel T-cell-specific immunophilin capable of calcineurin inhibition. Mol. Cell Biol. 15, 4395\u20134402 (1995).","journal-title":"Mol. Cell Biol."},{"key":"e_1_3_4_13_2","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/ncb1086","article-title":"A physical and functional map of the human TNF-alpha\/NF-kappa B signal transduction pathway","volume":"6","author":"Bouwmeester T.","year":"2004","unstructured":"T. Bouwmeester ., A physical and functional map of the human TNF-alpha\/NF-kappa B signal transduction pathway. Nat. Cell Biol. 6, 97\u2013105 (2004).","journal-title":"Nat. Cell Biol."},{"key":"e_1_3_4_14_2","doi-asserted-by":"crossref","first-page":"26263","DOI":"10.1074\/jbc.M114.582882","article-title":"NF-\u03baB transcriptional activity is modulated by FK506-binding proteins FKBP51 and FKBP52: A role for peptidyl-prolyl isomerase activity","volume":"289","author":"Erlejman A. G.","year":"2014","unstructured":"A. G. Erlejman ., NF-\u03baB transcriptional activity is modulated by FK506-binding proteins FKBP51 and FKBP52: A role for peptidyl-prolyl isomerase activity. J. Biol. Chem. 289, 26263\u201326276 (2014).","journal-title":"J. Biol. Chem."},{"key":"e_1_3_4_15_2","doi-asserted-by":"crossref","first-page":"4226","DOI":"10.4049\/jimmunol.1103040","article-title":"Functional changes in myeloid-derived suppressor cells (MDSCs) during tumor growth: FKBP51 contributes to the regulation of the immunosuppressive function of MDSCs","volume":"188","author":"Kim Y. S.","year":"2012","unstructured":"Y. S. Kim ., Functional changes in myeloid-derived suppressor cells (MDSCs) during tumor growth: FKBP51 contributes to the regulation of the immunosuppressive function of MDSCs. J. Immunol. 188, 4226\u20134234 (2012).","journal-title":"J. Immunol."},{"key":"e_1_3_4_16_2","doi-asserted-by":"crossref","first-page":"325ra19","DOI":"10.1126\/scitranslmed.aab3376","article-title":"The stress regulator FKBP51 drives chronic pain by modulating spinal glucocorticoid signaling","volume":"8","author":"Maiar\u00f9 M.","year":"2016","unstructured":"M. Maiar\u00f9 ., The stress regulator FKBP51 drives chronic pain by modulating spinal glucocorticoid signaling. Sci. Transl. Med. 8, 325ra19 (2016).","journal-title":"Sci. Transl. Med."},{"key":"e_1_3_4_17_2","doi-asserted-by":"crossref","first-page":"2829","DOI":"10.1016\/j.ejca.2004.08.017","article-title":"Rapamycin inhibits doxorubicin-induced NF-kappaB\/Rel nuclear activity and enhances the apoptosis of melanoma cells","volume":"40","author":"Romano M. F.","year":"2004","unstructured":"M. F. Romano ., Rapamycin inhibits doxorubicin-induced NF-kappaB\/Rel nuclear activity and enhances the apoptosis of melanoma cells. Eur. J. Cancer 40, 2829\u20132836 (2004).","journal-title":"Eur. J. Cancer"},{"key":"e_1_3_4_18_2","doi-asserted-by":"crossref","first-page":"6983","DOI":"10.1093\/nar\/gkv615","article-title":"FKBP51 employs both scaffold and isomerase functions to promote NF-\u03baB activation in melanoma","volume":"43","author":"Romano S.","year":"2015","unstructured":"S. Romano ., FKBP51 employs both scaffold and isomerase functions to promote NF-\u03baB activation in melanoma. Nucleic Acids Res. 43, 6983\u20136993 (2015).","journal-title":"Nucleic Acids Res."},{"key":"e_1_3_4_19_2","doi-asserted-by":"crossref","first-page":"1772","DOI":"10.1038\/bjc.2015.154","article-title":"Interleukin-8 is a key mediator of FKBP51-induced melanoma growth, angiogenesis and metastasis","volume":"112","author":"Srivastava S. K.","year":"2015","unstructured":"S. K. Srivastava ., Interleukin-8 is a key mediator of FKBP51-induced melanoma growth, angiogenesis and metastasis. Br. J. Cancer 112, 1772\u20131781 (2015).","journal-title":"Br. J. Cancer"},{"key":"e_1_3_4_20_2","doi-asserted-by":"crossref","first-page":"4158","DOI":"10.1172\/JCI69003","article-title":"Accelerated neurodegeneration through chaperone-mediated oligomerization of tau","volume":"123","author":"Blair L. J.","year":"2013","unstructured":"L. J. Blair ., Accelerated neurodegeneration through chaperone-mediated oligomerization of tau. J. Clin. Invest. 123, 4158\u20134169 (2013).","journal-title":"J. Clin. Invest."},{"key":"e_1_3_4_21_2","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1523\/JNEUROSCI.4815-09.2010","article-title":"The Hsp90 cochaperone, FKBP51, increases Tau stability and polymerizes microtubules","volume":"30","author":"Jinwal U. K.","year":"2010","unstructured":"U. K. Jinwal ., The Hsp90 cochaperone, FKBP51, increases Tau stability and polymerizes microtubules. J. Neurosci. 30, 591\u2013599 (2010).","journal-title":"J. Neurosci."},{"key":"e_1_3_4_22_2","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1038\/mp.2017.35","article-title":"Epigenetic programming by stress and glucocorticoids along the human lifespan","volume":"22","author":"Zannas A. S.","year":"2017","unstructured":"A. S. Zannas, G. P. Chrousos, Epigenetic programming by stress and glucocorticoids along the human lifespan. Mol. Psychiatry 22, 640\u2013646 (2017).","journal-title":"Mol. Psychiatry"},{"key":"e_1_3_4_23_2","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1186\/s13059-015-0828-5","article-title":"Lifetime stress accelerates epigenetic aging in an urban, African American cohort: Relevance of glucocorticoid signaling","volume":"16","author":"Zannas A. S.","year":"2015","unstructured":"A. S. Zannas ., Lifetime stress accelerates epigenetic aging in an urban, African American cohort: Relevance of glucocorticoid signaling. Genome Biol. 16, 266 (2015).","journal-title":"Genome Biol."},{"key":"e_1_3_4_24_2","doi-asserted-by":"crossref","first-page":"R115","DOI":"10.1186\/gb-2013-14-10-r115","article-title":"DNA methylation age of human tissues and cell types","volume":"14","author":"Horvath S.","year":"2013","unstructured":"S. Horvath DNA methylation age of human tissues and cell types. Genome Biol. 14, R115 (2013).","journal-title":"Genome Biol."},{"key":"e_1_3_4_25_2","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/s41576-018-0004-3","article-title":"DNA methylation-based biomarkers and the epigenetic clock theory of ageing","volume":"19","author":"Horvath S.","year":"2018","unstructured":"S. Horvath, K. Raj, DNA methylation-based biomarkers and the epigenetic clock theory of ageing. Nat. Rev. Genet. 19, 371\u2013384 (2018).","journal-title":"Nat. Rev. Genet."},{"key":"e_1_3_4_26_2","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/nn.3275","article-title":"Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions","volume":"16","author":"Klengel T.","year":"2013","unstructured":"T. Klengel ., Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions. Nat. Neurosci. 16, 33\u201341 (2013).","journal-title":"Nat. Neurosci."},{"key":"e_1_3_4_27_2","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.biopsych.2015.08.005","article-title":"Holocaust exposure induced intergenerational effects on FKBP5 methylation","volume":"80","author":"Yehuda R.","year":"2016","unstructured":"R. Yehuda ., Holocaust exposure induced intergenerational effects on FKBP5 methylation. Biol. Psychiatry 80, 372\u2013380 (2016).","journal-title":"Biol. Psychiatry"},{"key":"e_1_3_4_28_2","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/npp.2015.235","article-title":"Gene-stress-epigenetic regulation of FKBP5: Clinical and translational implications","volume":"41","author":"Zannas A. S.","year":"2016","unstructured":"A. S. Zannas, T. Wiechmann, N. C. Gassen, E. B. Binder, Gene-stress-epigenetic regulation of FKBP5: Clinical and translational implications. Neuropsychopharmacology 41, 261\u2013274 (2016).","journal-title":"Neuropsychopharmacology"},{"key":"e_1_3_4_29_2","doi-asserted-by":"crossref","first-page":"10522","DOI":"10.1073\/pnas.1120658109","article-title":"Distinct DNA methylomes of newborns and centenarians","volume":"109","author":"Heyn H.","year":"2012","unstructured":"H. Heyn ., Distinct DNA methylomes of newborns and centenarians. Proc. Natl. Acad. Sci. U.S.A. 109, 10522\u201310527 (2012).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"e_1_3_4_30_2","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.cell.2013.05.039","article-title":"The hallmarks of aging","volume":"153","author":"L\u00f3pez-Ot\u00edn C.","year":"2013","unstructured":"C. L\u00f3pez-Ot\u00edn, M. A. Blasco, L. Partridge, M. Serrano, G. Kroemer, The hallmarks of aging. Cell 153, 1194\u20131217 (2013).","journal-title":"Cell"},{"key":"e_1_3_4_31_2","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1111\/sji.12413","article-title":"Effects of ageing on the immune system: Infants to elderly","volume":"83","author":"Valiathan R.","year":"2016","unstructured":"R. Valiathan, M. Ashman, D. Asthana, Effects of ageing on the immune system: Infants to elderly. Scand. J. Immunol. 83, 255\u2013266 (2016).","journal-title":"Scand. J. Immunol."},{"key":"e_1_3_4_32_2","doi-asserted-by":"crossref","first-page":"R31","DOI":"10.1186\/gb-2014-15-2-r31","article-title":"Accounting for cellular heterogeneity is critical in epigenome-wide association studies","volume":"15","author":"Jaffe A. E.","year":"2014","unstructured":"A. E. Jaffe, R. A. Irizarry, Accounting for cellular heterogeneity is critical in epigenome-wide association studies. Genome Biol. 15, R31 (2014).","journal-title":"Genome Biol."},{"key":"e_1_3_4_33_2","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.molcel.2016.03.019","article-title":"Methylome-wide analysis of chronic HIV infection reveals five-year increase in biological age and epigenetic targeting of HLA","volume":"62","author":"Gross A. M.","year":"2016","unstructured":"A. M. Gross ., Methylome-wide analysis of chronic HIV infection reveals five-year increase in biological age and epigenetic targeting of HLA. Mol. Cell 62, 157\u2013168 (2016).","journal-title":"Mol. Cell"},{"key":"e_1_3_4_34_2","doi-asserted-by":"crossref","first-page":"4332","DOI":"10.1210\/en.2010-0225","article-title":"Chronic corticosterone exposure increases expression and decreases deoxyribonucleic acid methylation of Fkbp5 in mice","volume":"151","author":"Lee R. S.","year":"2010","unstructured":"R. S. Lee ., Chronic corticosterone exposure increases expression and decreases deoxyribonucleic acid methylation of Fkbp5 in mice. Endocrinology 151, 4332\u20134343 (2010).","journal-title":"Endocrinology"},{"key":"e_1_3_4_35_2","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/s00213-011-2307-3","article-title":"A measure of glucocorticoid load provided by DNA methylation of Fkbp5 in mice","volume":"218","author":"Lee R. S.","year":"2011","unstructured":"R. S. Lee ., A measure of glucocorticoid load provided by DNA methylation of Fkbp5 in mice. Psychopharmacology (Berl.) 218, 303\u2013312 (2011).","journal-title":"Psychopharmacology (Berl.)"},{"key":"e_1_3_4_36_2","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1038\/mp.2011.26","article-title":"Antidepressants increase human hippocampal neurogenesis by activating the glucocorticoid receptor","volume":"16","author":"Anacker C.","year":"2011","unstructured":"C. Anacker ., Antidepressants increase human hippocampal neurogenesis by activating the glucocorticoid receptor. Mol. Psychiatry 16, 738\u2013750 (2011).","journal-title":"Mol. Psychiatry"},{"key":"e_1_3_4_37_2","doi-asserted-by":"crossref","first-page":"2405","DOI":"10.1074\/jbc.M505625200","article-title":"Down-regulation of endogenous amyloid precursor protein processing due to cellular aging","volume":"281","author":"Kern A.","year":"2006","unstructured":"A. Kern, B. Roempp, K. Prager, J. Walter, C. Behl, Down-regulation of endogenous amyloid precursor protein processing due to cellular aging. J. Biol. Chem. 281, 2405\u20132413 (2006).","journal-title":"J. Biol. Chem."},{"key":"e_1_3_4_38_2","doi-asserted-by":"crossref","first-page":"6689","DOI":"10.1128\/MCB.22.19.6689-6696.2002","article-title":"DNA methylation has a local effect on transcription and histone acetylation","volume":"22","author":"Irvine R. A.","year":"2002","unstructured":"R. A. Irvine, I. G. Lin, C. L. Hsieh, DNA methylation has a local effect on transcription and histone acetylation. Mol. Cell Biol. 22, 6689\u20136696 (2002).","journal-title":"Mol. Cell Biol."},{"key":"e_1_3_4_39_2","doi-asserted-by":"crossref","first-page":"e17490","DOI":"10.1371\/journal.pone.0017490","article-title":"Integrated analysis of gene expression, CpG island methylation, and gene copy number in breast cancer cells by deep sequencing","volume":"6","author":"Sun Z.","year":"2011","unstructured":"Z. Sun ., Integrated analysis of gene expression, CpG island methylation, and gene copy number in breast cancer cells by deep sequencing. PLoS One 6, e17490 (2011).","journal-title":"PLoS One"},{"key":"e_1_3_4_40_2","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/nmeth.1906","article-title":"ChromHMM: Automating chromatin-state discovery and characterization","volume":"9","author":"Ernst J.","year":"2012","unstructured":"J. Ernst, M. Kellis, ChromHMM: Automating chromatin-state discovery and characterization. Nat. Methods 9, 215\u2013216 (2012).","journal-title":"Nat. Methods"},{"key":"e_1_3_4_41_2","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1016\/j.molcel.2013.01.038","article-title":"Modification of enhancer chromatin: What, how, and why?","volume":"49","author":"Calo E.","year":"2013","unstructured":"E. Calo, J. Wysocka, Modification of enhancer chromatin: What, how, and why? Mol. Cell 49, 825\u2013837 (2013).","journal-title":"Mol. Cell"},{"key":"e_1_3_4_42_2","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s13072-015-0014-8","article-title":"Wanderer, an interactive viewer to explore DNA methylation and gene expression data in human cancer","volume":"8","author":"D\u00edez-Villanueva A.","year":"2015","unstructured":"A. D\u00edez-Villanueva, I. Mallona, M. A. Peinado, Wanderer, an interactive viewer to explore DNA methylation and gene expression data in human cancer. Epigenetics Chromatin 8, 22 (2015).","journal-title":"Epigenetics Chromatin"},{"key":"e_1_3_4_43_2","doi-asserted-by":"crossref","unstructured":"A. Menke . Dexamethasone stimulated gene expression in peripheral blood is a sensitive marker for glucocorticoid receptor resistance in depressed patients. Neuropsychopharmacology 37 1455\u20131464 (2012). Erratum in: Neuropsychopharmacology 37 1972 (2012).","DOI":"10.1038\/npp.2011.331"},{"key":"e_1_3_4_44_2","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.atherosclerosis.2014.03.003","article-title":"Neutrophil to lymphocyte ratio in relation to risk of all-cause mortality and cardiovascular events among patients undergoing angiography or cardiac revascularization: A meta-analysis of observational studies","volume":"234","author":"Wang X.","year":"2014","unstructured":"X. Wang ., Neutrophil to lymphocyte ratio in relation to risk of all-cause mortality and cardiovascular events among patients undergoing angiography or cardiac revascularization: A meta-analysis of observational studies. Atherosclerosis 234, 206\u2013213 (2014).","journal-title":"Atherosclerosis"},{"key":"e_1_3_4_45_2","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1586\/erc.12.159","article-title":"Neutrophil to lymphocyte ratio and cardiovascular diseases: A review","volume":"11","author":"Bhat T.","year":"2013","unstructured":"T. Bhat ., Neutrophil to lymphocyte ratio and cardiovascular diseases: A review. Expert Rev. Cardiovasc. Ther. 11, 55\u201359 (2013).","journal-title":"Expert Rev. Cardiovasc. Ther."},{"key":"e_1_3_4_46_2","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1002\/jlb.56.5.559","article-title":"Essential involvement of interleukin-8 (IL-8) in acute inflammation","volume":"56","author":"Harada A.","year":"1994","unstructured":"A. Harada ., Essential involvement of interleukin-8 (IL-8) in acute inflammation. J. Leukoc. Biol. 56, 559\u2013564 (1994).","journal-title":"J. Leukoc. Biol."},{"key":"e_1_3_4_47_2","doi-asserted-by":"crossref","first-page":"3792","DOI":"10.1073\/pnas.95.7.3792","article-title":"NF-kappaB-inducing kinase activates IKK-alpha by phosphorylation of Ser-176","volume":"95","author":"Ling L.","year":"1998","unstructured":"L. Ling, Z. Cao, D. V. Goeddel, NF-kappaB-inducing kinase activates IKK-alpha by phosphorylation of Ser-176. Proc. Natl. Acad. Sci. U.S.A. 95, 3792\u20133797 (1998).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"e_1_3_4_48_2","doi-asserted-by":"crossref","first-page":"a000034","DOI":"10.1101\/cshperspect.a000034","article-title":"The NF-kappaB family of transcription factors and its regulation","volume":"1","author":"Oeckinghaus A.","year":"2009","unstructured":"A. Oeckinghaus, S. Ghosh, The NF-kappaB family of transcription factors and its regulation. Cold Spring Harb. Perspect. Biol. 1, a000034 (2009).","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"e_1_3_4_49_2","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/nchembio.1699","article-title":"Selective inhibitors of the FK506-binding protein 51 by induced fit","volume":"11","author":"Gaali S.","year":"2015","unstructured":"S. Gaali ., Selective inhibitors of the FK506-binding protein 51 by induced fit. Nat. Chem. Biol. 11, 33\u201337 (2015).","journal-title":"Nat. Chem. Biol."},{"key":"e_1_3_4_50_2","doi-asserted-by":"crossref","first-page":"127","DOI":"10.4161\/epi.1.3.3327","article-title":"Functional analysis of promoter CpG methylation using a CpG-free luciferase reporter vector","volume":"1","author":"Klug M.","year":"2006","unstructured":"M. Klug, M. Rehli, Functional analysis of promoter CpG methylation using a CpG-free luciferase reporter vector. Epigenetics 1, 127\u2013130 (2006).","journal-title":"Epigenetics"},{"key":"e_1_3_4_51_2","first-page":"Unit 1B.10","article-title":"The streptavidin\/biotinylated DNA\/protein bound complex protocol for determining the association of c-JUN protein with NANOG promoter","volume":"1","author":"Ibrahim E. E.","year":"2013","unstructured":"E. E. Ibrahim, R. Babaei-Jadidi, A. S. Nateri, (2013) The streptavidin\/biotinylated DNA\/protein bound complex protocol for determining the association of c-JUN protein with NANOG promoter. Curr. Protoc. Stem Cell Biol. Chapter 1, Unit 1B.10.","journal-title":"Curr. Protoc. Stem Cell Biol."},{"key":"e_1_3_4_52_2","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.1161\/CIRCRESAHA.114.302699","article-title":"Inflammation and its resolution as determinants of acute coronary syndromes","volume":"114","author":"Libby P.","year":"2014","unstructured":"P. Libby, I. Tabas, G. Fredman, E. A. Fisher, Inflammation and its resolution as determinants of acute coronary syndromes. Circ. Res. 114, 1867\u20131879 (2014).","journal-title":"Circ. Res."},{"key":"e_1_3_4_53_2","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1093\/biomet\/70.1.41","article-title":"The central role of the propensity score in observational studies for causal effects","volume":"70","author":"Rosenbaum P.","year":"1983","unstructured":"P. Rosenbaum, D. Rubin, The central role of the propensity score in observational studies for causal effects. Biometrika 70, 41\u201355 (1983).","journal-title":"Biometrika"},{"key":"e_1_3_4_54_2","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1093\/emboj\/20.8.1974","article-title":"Glucocorticoid-induced DNA demethylation and gene memory during development","volume":"20","author":"Thomassin H.","year":"2001","unstructured":"H. Thomassin, M. Flavin, M. L. Espin\u00e1s, T. Grange, Glucocorticoid-induced DNA demethylation and gene memory during development. EMBO J. 20, 1974\u20131983 (2001).","journal-title":"EMBO J."},{"key":"e_1_3_4_55_2","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s13072-018-0209-x","article-title":"HAM-TBS: High-accuracy methylation measurements via targeted bisulfite sequencing","volume":"11","author":"Roeh S.","year":"2018","unstructured":"S. Roeh ., HAM-TBS: High-accuracy methylation measurements via targeted bisulfite sequencing. Epigenetics Chromatin 11, 39 (2018).","journal-title":"Epigenetics Chromatin"},{"key":"e_1_3_4_56_2","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1161\/01.ATV.0000134294.54422.2e","article-title":"IL-8 plasma concentrations and the risk of future coronary artery disease in apparently healthy men and women: The EPIC-norfolk prospective population study","volume":"24","author":"Boekholdt S. M.","year":"2004","unstructured":"S. M. Boekholdt ., IL-8 plasma concentrations and the risk of future coronary artery disease in apparently healthy men and women: The EPIC-norfolk prospective population study. Arterioscler. Thromb. Vasc. Biol. 24, 1503\u20131508 (2004).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"e_1_3_4_57_2","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.atherosclerosis.2015.08.022","article-title":"Elevated baseline plasma IL-8 levels are an independent predictor of long-term all-cause mortality in patients with acute coronary syndrome","volume":"242","author":"Cavusoglu E.","year":"2015","unstructured":"E. Cavusoglu ., Elevated baseline plasma IL-8 levels are an independent predictor of long-term all-cause mortality in patients with acute coronary syndrome. Atherosclerosis 242, 589\u2013594 (2015).","journal-title":"Atherosclerosis"},{"key":"e_1_3_4_58_2","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1136\/bmj.38693.435301.80","article-title":"Chronic stress at work and the metabolic syndrome: Prospective study","volume":"332","author":"Chandola T.","year":"2006","unstructured":"T. Chandola, E. Brunner, M. Marmot, Chronic stress at work and the metabolic syndrome: Prospective study. BMJ 332, 521\u2013525 (2006).","journal-title":"BMJ"},{"key":"e_1_3_4_59_2","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1016\/j.jacc.2013.04.085","article-title":"Post-traumatic stress disorder and incidence of coronary heart disease: A twin study","volume":"62","author":"Vaccarino V.","year":"2013","unstructured":"V. Vaccarino ., Post-traumatic stress disorder and incidence of coronary heart disease: A twin study. J. Am. Coll. Cardiol. 62, 970\u2013978 (2013).","journal-title":"J. Am. Coll. Cardiol."},{"key":"e_1_3_4_60_2","unstructured":"K. Ressler A. Smith E. Binder V. Kilaru DNA Methylation of African Americans from the Grady Trauma Project. Gene Expression Omnibus (GEO). https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE72680. Deposited 3 September 2015."},{"key":"e_1_3_4_61_2","unstructured":"J. Arloth E. B. Binder Epigenome analysis of depressed and control subjects. [subset]. Gene Expression Omnibus (GEO). https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE128235. Deposited 13 March 2019."},{"key":"e_1_3_4_62_2","unstructured":"D. Mehta Transcriptional landscape of aging in humans. Gene Expression Omnibus (GEO). https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE58137. Deposited 2 June 2014."},{"key":"e_1_3_4_63_2","unstructured":"A. Zannas \u201cEpigenetic mechanisms linking psychological stress and aging-related disease \u201d dissertation Ludwig Maximilians University of Munich (2017)."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.1816847116","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1816847116","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T15:39:01Z","timestamp":1654616341000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1816847116"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,21]]},"references-count":63,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2019,6,4]]}},"alternative-id":["10.1073\/pnas.1816847116"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1816847116","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,21]]},"assertion":[{"value":"2019-05-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}