{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T23:13:28Z","timestamp":1789859608842,"version":"4.0.1"},"reference-count":44,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2014,9,5]],"date-time":"2014-09-05T00:00:00Z","timestamp":1409875200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0107241","type":"journal-article","created":{"date-parts":[[2014,9,5]],"date-time":"2014-09-05T15:04:46Z","timestamp":1409929486000},"page":"e107241","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":100,"title":["Age-Associated Epigenetic Upregulation of the FKBP5 Gene Selectively Impairs Stress Resiliency"],"prefix":"10.1371","volume":"9","author":[{"given":"Jonathan J.","family":"Sabbagh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"O'Leary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura J.","family":"Blair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torsten","family":"Klengel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryce A.","family":"Nordhues","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah N.","family":"Fontaine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth B.","family":"Binder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad A.","family":"Dickey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2014,9,5]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1111\/j.1532-5415.2005.53202.x","article-title":"The course of functional decline in older people with persistently elevated depressive symptoms: longitudinal findings from the Cardiovascular Health Study","volume":"53","author":"EJ Lenze","year":"2005","journal-title":"J Am Geriatr Soc"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1161\/01.STR.0000149626.50127.d0","article-title":"Depressive symptoms and mortality in men: results from the Multiple Risk Factor Intervention Trial","volume":"36","author":"BB Gump","year":"2005","journal-title":"Stroke"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1002\/da.20686","article-title":"Depression gets old fast: do stress and depression accelerate cell aging?","volume":"27","author":"OM Wolkowitz","year":"2010","journal-title":"Depress Anxiety"},{"key":"ref4","article-title":"Mechanisms underlying the neuroprotective effect of brain reserve against late life depression","author":"T Freret","year":"2014","journal-title":"J Neural Transm"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"e24840","DOI":"10.1371\/journal.pone.0024840","article-title":"A new anti-depressive strategy for the elderly: ablation of FKBP5\/FKBP51","volume":"6","author":"JC O'Leary 3rd","year":"2011","journal-title":"PLoS One"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1016\/j.biopsych.2011.07.023","article-title":"FK506 binding protein 5 shapes stress responsiveness: modulation of neuroendocrine reactivity and coping behavior","volume":"70","author":"C Touma","year":"2011","journal-title":"Biol Psychiatry"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"4158","DOI":"10.1172\/JCI69003","article-title":"Accelerated neurodegeneration through chaperone-mediated oligomerization of tau","volume":"123","author":"LJ Blair","year":"2013","journal-title":"J Clin Invest"},{"key":"ref8","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":"UK Jinwal","year":"2010","journal-title":"J Neurosci"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1001\/jama.299.11.1291","article-title":"Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults","volume":"299","author":"EB Binder","year":"2008","journal-title":"JAMA"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1038\/ng1479","article-title":"Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment","volume":"36","author":"EB Binder","year":"2004","journal-title":"Nat Genet"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1002\/da.22158","article-title":"Role of allelic variants of FK506-binding protein 51 (FKBP5) gene in the development of anxiety disorders","volume":"30","author":"A Minelli","year":"2013","journal-title":"Depress Anxiety"},{"key":"ref12","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":"T Klengel","year":"2013","journal-title":"Nat Neurosci"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1111\/j.1471-4159.2012.07775.x","article-title":"Regulation of the glucocorticoid response to stress-related disorders by the Hsp90-binding immunophilin FKBP51","volume":"122","author":"NM Galigniana","year":"2012","journal-title":"J Neurochem"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"4107","DOI":"10.1210\/endo.141.11.7785","article-title":"Squirrel monkey immunophilin FKBP51 is a potent inhibitor of glucocorticoid receptor binding","volume":"141","author":"WB Denny","year":"2000","journal-title":"Endocrinology"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"4609","DOI":"10.1074\/jbc.M407498200","article-title":"FK506-binding proteins 51 and 52 differentially regulate dynein interaction and nuclear translocation of the glucocorticoid receptor in mammalian cells","volume":"280","author":"GM Wochnik","year":"2005","journal-title":"J Biol Chem"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.neuropharm.2011.07.041","article-title":"The involvement of FK506-binding protein 51 (FKBP5) in the behavioral and neuroendocrine effects of chronic social defeat stress","volume":"62","author":"J Hartmann","year":"2012","journal-title":"Neuropharmacology"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/j.biopsych.2005.09.008","article-title":"Glucocorticoids and relapse of major depression (dexamethasone\/corticotropin-releasing hormone test in relation to relapse of major depression)","volume":"59","author":"BC Appelhof","year":"2006","journal-title":"Biol Psychiatry"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1016\/j.psyneuen.2011.10.005","article-title":"Longitudinal hypothalamic-pituitary-adrenal axis trait and state effects in recurrent depression","volume":"37","author":"A Lok","year":"2012","journal-title":"Psychoneuroendocrinology"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0022-3956(01)00013-9","article-title":"Cortisol response in the combined dexamethasone\/CRH test as predictor of relapse in patients with remitted depression. a prospective study","volume":"35","author":"AW Zobel","year":"2001","journal-title":"J Psychiatr Res"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/0047-6374(94)01529-U","article-title":"Strain, stress, neurodegeneration and longevity","volume":"78","author":"GM Gilad","year":"1995","journal-title":"Mech Ageing Dev"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"E987","DOI":"10.1152\/ajpendo.00474.2011","article-title":"Hypothalamic Fkbp51 is induced by fasting, and elevated hypothalamic expression promotes obese phenotypes","volume":"302","author":"L Yang","year":"2012","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.tem.2011.08.001","article-title":"FKBP51 and FKBP52 in signaling and disease","volume":"22","author":"CL Storer","year":"2011","journal-title":"Trends Endocrinol Metab"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1001\/2013.jamapsychiatry.210","article-title":"FKBP5 and attention bias for threat: associations with hippocampal function and shape","volume":"70","author":"N Fani","year":"2013","journal-title":"JAMA Psychiatry"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1210\/en.2005-1001","article-title":"Direct, androgen receptor-mediated regulation of the FKBP5 gene via a distal enhancer element","volume":"147","author":"JA Magee","year":"2006","journal-title":"Endocrinology"},{"key":"ref25","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":"RS Lee","year":"2010","journal-title":"Endocrinology"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1038\/nature09938","article-title":"Neuropsin cleaves EphB2 in the amygdala to control anxiety","volume":"473","author":"BK Attwood","year":"2011","journal-title":"Nature"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/j.pnpbp.2010.03.005","article-title":"Behavioral and neurobiological consequences of prolonged glucocorticoid exposure in rats: relevance to depression","volume":"34","author":"EY Sterner","year":"2010","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"17312","DOI":"10.1073\/pnas.0407162101","article-title":"Accelerated telomere shortening in response to life stress","volume":"101","author":"ES Epel","year":"2004","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/j.biopsych.2006.02.004","article-title":"Telomere shortening and mood disorders: preliminary support for a chronic stress model of accelerated aging","volume":"60","author":"NM Simon","year":"2006","journal-title":"Biol Psychiatry"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1055\/s-2000-7742","article-title":"Major depression and impaired glucose tolerance","volume":"108","author":"B Weber","year":"2000","journal-title":"Exp Clin Endocrinol Diabetes"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1159\/000314272","article-title":"Metabolic syndrome in Cushing's syndrome","volume":"92","author":"P Chanson","year":"2010","journal-title":"Neuroendocrinology"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1210\/en.2009-1436","article-title":"Endocrine and physiological changes in response to chronic corticosterone: a potential model of the metabolic syndrome in mouse","volume":"151","author":"IN Karatsoreos","year":"2010","journal-title":"Endocrinology"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.coph.2011.04.011","article-title":"FKBP51 and the NF-kappaB regulatory pathway in cancer","volume":"11","author":"S Romano","year":"2011","journal-title":"Curr Opin Pharmacol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.ejphar.2013.02.006","article-title":"Effects of milnacipran on cognitive flexibility following chronic stress in rats","volume":"703","author":"KJ Naegeli","year":"2013","journal-title":"Eur J Pharmacol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.neuroscience.2011.07.014","article-title":"Chronic stress modulates neural and cardiovascular responses during reversal learning","volume":"193","author":"H Ohira","year":"2011","journal-title":"Neuroscience"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"2164","DOI":"10.1016\/j.neurobiolaging.2013.03.019","article-title":"Distinct manifestations of executive dysfunction in aged rats","volume":"34","author":"BS Beas","year":"2013","journal-title":"Neurobiol Aging"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1037\/0033-2909.120.2.272","article-title":"An application of prefrontal cortex function theory to cognitive aging","volume":"120","author":"RL West","year":"1996","journal-title":"Psychol Bull"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/j.bbrc.2012.03.035","article-title":"Glucocorticoid-induced loss of DNA methylation in non-neuronal cells and potential involvement of DNMT1 in epigenetic regulation of Fkbp5","volume":"420","author":"X Yang","year":"2012","journal-title":"Biochem Biophys Res Commun"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1001\/archpsyc.65.12.1394","article-title":"Incidence and recurrence of late-life depression","volume":"65","author":"HJ Luijendijk","year":"2008","journal-title":"Arch Gen Psychiatry"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.pneurobio.2012.05.009","article-title":"The neurobiology of depression in later-life: clinical, neuropsychological, neuroimaging and pathophysiological features","volume":"98","author":"SL Naismith","year":"2012","journal-title":"Prog Neurobiol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3233\/JAD-2010-1352","article-title":"Neuropsychiatric predictors of progression from amnestic-mild cognitive impairment to Alzheimer's disease: the role of depression and apathy","volume":"20","author":"K Palmer","year":"2010","journal-title":"J Alzheimers Dis"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1080\/09540260802094480","article-title":"Depression in Alzheimer's disease: phenomenology, clinical correlates and treatment","volume":"20","author":"SE Starkstein","year":"2008","journal-title":"International review of psychiatry (Abingdon, England)"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1002\/cmdc.201200137","article-title":"The prospect of FKBP51 as a drug target","volume":"7","author":"MV Schmidt","year":"2012","journal-title":"ChemMedChem"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1038\/nprot.2006.275","article-title":"Two-day radial-arm water maze learning and memory task; robust resolution of amyloid-related memory deficits in transgenic mice","volume":"1","author":"J Alamed","year":"2006","journal-title":"Nat Protoc"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0107241","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,8,14]],"date-time":"2019-08-14T14:23:31Z","timestamp":1565792611000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0107241"}},"subtitle":[],"editor":[{"given":"Takeo","family":"Yoshikawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2014,9,5]]},"references-count":44,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2014,9,5]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0107241","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,9,5]]}}}