{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T23:30:40Z","timestamp":1790206240044,"version":"4.1.0"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2018,12,26]],"date-time":"2018-12-26T00:00:00Z","timestamp":1545782400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AG020628"],"award-info":[{"award-number":["AG020628"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AG028268"],"award-info":[{"award-number":["AG028268"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL58984"],"award-info":[{"award-number":["HL58984"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Michigan Research Career Development core"},{"name":"Claude D. Pepper Older American Independence Center","award":["AG024824"],"award-info":[{"award-number":["AG024824"]}]},{"name":"Claude D. Pepper Older American Independence Center","award":["DK020572"],"award-info":[{"award-number":["DK020572"]}]},{"name":"MDRC","award":["DK089503"],"award-info":[{"award-number":["DK089503"]}]},{"name":"MNORC","award":["1U2CDK110678-01"],"award-info":[{"award-number":["1U2CDK110678-01"]}]},{"name":"UM-MMPC"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,10,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Visceral adipose tissue (VAT) inflammation plays a central role in longevity and multiple age-related disorders. Cellular senescence (SEN) is a fundamental aging mechanism that contributes to age-related chronic inflammation and organ dysfunction, including VAT. Recent studies using heterochronic parabiosis models strongly suggested that circulating factors in young plasma alter the aging phenotypes of old animals. Our study investigated if young plasma rescued SEN phenotypes in the VAT of aging mice. With heterochronic parabiosis model using young (3 months) and old (18 months) mice, we found significant reduction in the levels of pro-inflammatory cytokines and altered adipokine profile that are protective of SEN in the VAT of old mice. These data are indicative of protection from SEN of aging VAT by young blood circulation. Old parabionts also exhibited diminished expression of cyclin-dependent kinase inhibitors (CDKi) genes p16 (Cdkn2a) and p21 (Cdkn1a\/Cip1) in the VAT. In addition, when exposed to young serum condition in an ex vivo culture system, aging adipose tissue\u2013derived stromovascular fraction cells produced significantly lower amounts of pro-inflammatory cytokines (MCP-1 and IL-6) compared to old condition. Expressions of p16 and p21 genes were also diminished in the old stromovascular fraction cells under young serum condition. Finally, in 3T3-preadipocytes culture system, we found reduced pro-inflammatory cytokines (Mcp-1 and Il-6) and diminished expression of cyclin-dependent kinase inhibitor genes in the presence of young serum compared to old serum. In summary, this study demonstrates that young milieu is capable of protecting aging adipose tissue from SEN and thereby inflammation.<\/jats:p>","DOI":"10.1093\/gerona\/gly290","type":"journal-article","created":{"date-parts":[[2018,12,26]],"date-time":"2018-12-26T09:58:25Z","timestamp":1545818305000},"page":"1709-1715","source":"Crossref","is-referenced-by-count":71,"title":["Adipose Tissue Senescence and Inflammation in Aging is Reversed by the Young Milieu"],"prefix":"10.1093","volume":"74","author":[{"given":"Amiya Kumar","family":"Ghosh","sequence":"first","affiliation":[{"name":"Division of Geriatric and Palliative Medicine, University of Michigan, Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"Division of Geriatric and Palliative Medicine, University of Michigan, Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Mau","sequence":"additional","affiliation":[{"name":"Division of Geriatric and Palliative Medicine, University of Michigan, Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Qi","sequence":"additional","affiliation":[{"name":"Animal Phenotyping Core, Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond","family":"Yung","sequence":"additional","affiliation":[{"name":"Division of Geriatric and Palliative Medicine, University of Michigan, Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,12,26]]},"reference":[{"key":"2019100406463217800_CIT0001","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1093\/gerona\/glp213","article-title":"Aging, depot origin, and preadipocyte gene expression","volume":"65","author":"Cartwright","year":"2010","journal-title":"J Gerontol A Biol Sci Med Sci."},{"key":"2019100406463217800_CIT0002","doi-asserted-by":"publisher","first-page":"256","DOI":"10.18632\/aging.100738","article-title":"High-fat diet induced obesity primes inflammation in adipose tissue prior to liver in C57BL\/6j mice","volume":"7","author":"van der Heijden","year":"2015","journal-title":"Aging (Albany NY)."},{"key":"2019100406463217800_CIT0003","doi-asserted-by":"crossref","first-page":"B89","DOI":"10.1093\/gerona\/54.3.B89","article-title":"Revisiting the role of fat mass in the life extension induced by caloric restriction","volume":"54","author":"Barzilai","year":"1999","journal-title":"J Gerontol A Biol Sci Med Sci."},{"key":"2019100406463217800_CIT0004","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1093\/gerona\/61.1.14","article-title":"Caloric restriction and aging: controversial issues","volume":"61","author":"Masoro","year":"2006","journal-title":"J Gerontol A Biol Sci Med Sci."},{"key":"2019100406463217800_CIT0005","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1126\/science.1078223299\/5606\/572","article-title":"Extended longevity in mice lacking the insulin receptor in adipose tissue","volume":"299","author":"Bluher","year":"2003","journal-title":"Science."},{"key":"2019100406463217800_CIT0006","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1126\/science.1177221","article-title":"Ribosomal protein S6 kinase 1 signaling regulates mammalian life span","volume":"326","author":"Selman","year":"2009","journal-title":"Science."},{"key":"2019100406463217800_CIT0007","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1254\/jphs.08215FP","article-title":"Rapamycin protects against high fat diet-induced obesity in C57BL\/6J mice","volume":"109","author":"Chang","year":"2009","journal-title":"J Pharmacol Sci."},{"key":"2019100406463217800_CIT0008","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1038\/nature08221","article-title":"Rapamycin fed late in life extends lifespan in genetically heterogeneous mice","volume":"460","author":"Harrison","year":"2009","journal-title":"Nature."},{"key":"2019100406463217800_CIT0009","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1111\/j.1474-9726.2008.00391.x","article-title":"Visceral adipose tissue modulates mammalian longevity","volume":"7","author":"Muzumdar","year":"2008","journal-title":"Aging Cell."},{"key":"2019100406463217800_CIT0010","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1111\/acel.12201","article-title":"The contribution of visceral fat to improved insulin signaling in Ames dwarf mice","volume":"13","author":"Menon","year":"2014","journal-title":"Aging Cell."},{"key":"2019100406463217800_CIT0011","doi-asserted-by":"publisher","first-page":"1320","DOI":"10.1093\/gerona\/glu186","article-title":"Elevated endoplasmic reticulum stress response contributes to adipose tissue inflammation in aging","volume":"70","author":"Ghosh","year":"2015","journal-title":"J Gerontol A Biol Sci Med Sci."},{"key":"2019100406463217800_CIT0012","doi-asserted-by":"publisher","first-page":"2525","DOI":"10.18632\/aging.101083","article-title":"Impaired autophagy activity is linked to elevated ER-stress and inflammation in aging adipose tissue","volume":"8","author":"Ghosh","year":"2016","journal-title":"Aging (Albany NY)."},{"key":"2019100406463217800_CIT0013","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1111\/j.1474-9726.2010.00608.x","article-title":"Fat tissue, aging, and cellular senescence","volume":"9","author":"Tchkonia","year":"2010","journal-title":"Aging Cell."},{"key":"2019100406463217800_CIT0014","doi-asserted-by":"publisher","first-page":"575","DOI":"10.18632\/aging.100681","article-title":"Growth hormone action predicts age-related white adipose tissue dysfunction and senescent cell burden in mice","volume":"6","author":"Stout","year":"2014","journal-title":"Aging (Albany NY)."},{"key":"2019100406463217800_CIT0015","doi-asserted-by":"publisher","first-page":"1971","DOI":"10.18632\/aging.101288","article-title":"Toll-like receptor 4 (TLR4) deficient mice are protected from adipose tissue inflammation in aging","volume":"9","author":"Ghosh","year":"2017","journal-title":"Aging (Albany NY)."},{"key":"2019100406463217800_CIT0016","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1126\/science.1251141","article-title":"Vascular and neurogenic rejuvenation of the aging mouse brain by young systemic factors","volume":"344","author":"Katsimpardi","year":"2014","journal-title":"Science."},{"key":"2019100406463217800_CIT0017","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1159\/000210677","article-title":"Parabiosis between old and young rats","volume":"1","author":"Mccay","year":"1957","journal-title":"Gerontologia."},{"key":"2019100406463217800_CIT0018","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1126\/science.1251152","article-title":"Restoring systemic GDF11 levels reverses age-related dysfunction in mouse skeletal muscle","volume":"344","author":"Sinha","year":"2014","journal-title":"Science."},{"key":"2019100406463217800_CIT0019","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1038\/nm.3898","article-title":"\u03b22-microglobulin is a systemic pro-aging factor that impairs cognitive function and neurogenesis","volume":"21","author":"Smith","year":"2015","journal-title":"Nat Med."},{"key":"2019100406463217800_CIT0020","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1111\/jnc.12969","article-title":"Aging and brain rejuvenation as systemic events","volume":"132","author":"Bouchard","year":"2015","journal-title":"J Neurochem."},{"key":"2019100406463217800_CIT0021","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1038\/nm.3569","article-title":"Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice","volume":"20","author":"Villeda","year":"2014","journal-title":"Nat Med."},{"key":"2019100406463217800_CIT0022","doi-asserted-by":"publisher","first-page":"6473","DOI":"10.1038\/ncomms7473","article-title":"Bmi1 limits dilated cardiomyopathy and heart failure by inhibiting cardiac senescence","volume":"6","author":"Gonzalez-Valdes","year":"2015","journal-title":"Nat Commun."},{"key":"2019100406463217800_CIT0023","doi-asserted-by":"publisher","first-page":"4784","DOI":"10.4049\/jimmunol.1403158","article-title":"Young, proliferative thymic epithelial cells engraft and function in aging thymuses","volume":"194","author":"Kim","year":"2015","journal-title":"J Immunol."},{"key":"2019100406463217800_CIT0024","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1093\/gerona\/glx183","article-title":"A young blood environment decreases aging of senile mice kidneys","volume":"73","author":"Huang","year":"2018","journal-title":"J Gerontol A Biol Sci Med Sci."},{"key":"2019100406463217800_CIT0025","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1016\/j.cmet.2015.05.010","article-title":"GDF11 increases with age and inhibits skeletal muscle regeneration","volume":"22","author":"Egerman","year":"2015","journal-title":"Cell Metab."},{"key":"2019100406463217800_CIT0026","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.jad.2014.12.010","article-title":"Increased serum levels of eotaxin\/CCL11 in late-stage patients with bipolar disorder: an accelerated aging biomarker","volume":"182","author":"Panizzutti","year":"2015","journal-title":"J Affect Disord."},{"key":"2019100406463217800_CIT0027","doi-asserted-by":"publisher","first-page":"402","DOI":"10.3389\/fnagi.2017.00402","article-title":"The \u201caging factor\u201d eotaxin-1 (CCL11) is detectable in transfusion blood products and increases with the donor\u2019s age","volume":"9","author":"Hoefer","year":"2017","journal-title":"Front Aging Neurosci."},{"key":"2019100406463217800_CIT0028","doi-asserted-by":"publisher","DOI":"10.3791\/50556","article-title":"Parabiosis in mice: a detailed protocol","author":"Kamran","year":"2013","journal-title":"J Vis Exp."},{"key":"2019100406463217800_CIT0029","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1016\/j.bmcl.2014.11.087","article-title":"Structure-based design, synthesis and biological evaluation of novel \u03b2-secretase inhibitors containing a pyrazole or thiazole moiety as the P3 ligand","volume":"25","author":"Ghosh","year":"2015","journal-title":"Bioorg Med Chem Lett."},{"key":"2019100406463217800_CIT0030","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1111\/j.1474-9726.2007.00315.x","article-title":"Regulation of replicative senescence by insulin-like growth factor-binding protein 3 in human umbilical vein endothelial cells","volume":"6","author":"Kim","year":"2007","journal-title":"Aging Cell."},{"key":"2019100406463217800_CIT0031","doi-asserted-by":"publisher","first-page":"4543","DOI":"10.1091\/mbc.e07-03-0280","article-title":"Induction of cellular senescence by insulin-like growth factor binding protein-5 through a p53-dependent mechanism","volume":"18","author":"Kim","year":"2007","journal-title":"Mol Biol Cell."},{"key":"2019100406463217800_CIT0032","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1007\/s10522-007-9084-8","article-title":"Heme oxygenase-1 and interleukin-11 are overexpressed in stress-induced premature senescence of human WI-38 fibroblasts induced by tert-butylhydroperoxide and ethanol","volume":"8","author":"Pascal","year":"2007","journal-title":"Biogerontology."},{"key":"2019100406463217800_CIT0033","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1038\/labinvest.3700241","article-title":"p53-dependent ICAM-1 overexpression in senescent human cells identified in atherosclerotic lesions","volume":"85","author":"Gorgoulis","year":"2005","journal-title":"Lab Invest."},{"key":"2019100406463217800_CIT0034","doi-asserted-by":"publisher","first-page":"e2188","DOI":"10.1038\/cddis.2016.68","article-title":"Leptin changes differentiation fate and induces senescence in chondrogenic progenitor cells","volume":"7","author":"Zhao","year":"2016","journal-title":"Cell Death Dis."},{"key":"2019100406463217800_CIT0035","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1128\/MCB.20.1.273-285.2000","article-title":"Regulation of a senescence checkpoint response by the E2F1 transcription factor and p14(ARF) tumor suppressor","volume":"20","author":"Dimri","year":"2000","journal-title":"Mol Cell Biol."},{"key":"2019100406463217800_CIT0036","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1096\/fj.201600832R","article-title":"IL-10 prevents aging-associated inflammation and insulin resistance in skeletal muscle","volume":"31","author":"Dagdeviren","year":"2017","journal-title":"FASEB J."},{"key":"2019100406463217800_CIT0037","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.exger.2014.10.012","article-title":"Clinical strategies and animal models for developing senolytic agents","volume":"68","author":"Kirkland","year":"2015","journal-title":"Exp Gerontol."},{"key":"2019100406463217800_CIT0038","doi-asserted-by":"publisher","first-page":"808","DOI":"10.4161\/auto.23922","article-title":"Autophagy and senescence: a partnership in search of definition","volume":"9","author":"Gewirtz","year":"2013","journal-title":"Autophagy."},{"key":"2019100406463217800_CIT0039","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1016\/j.mad.2008.04.001","article-title":"Cellular senescence and organismal aging","volume":"129","author":"Jeyapalan","year":"2008","journal-title":"Mech Ageing Dev."},{"key":"2019100406463217800_CIT0040","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1080\/15548627.2015.1121361","article-title":"How autophagy both activates and inhibits cellular senescence","volume":"12","author":"Kang","year":"2016","journal-title":"Autophagy."},{"key":"2019100406463217800_CIT0041","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1038\/nrm2233","article-title":"Cellular senescence: when bad things happen to good cells","volume":"8","author":"Campisi","year":"2007","journal-title":"Nat Rev Mol Cell Biol."},{"key":"2019100406463217800_CIT0042","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1038\/nature10600","article-title":"Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders","volume":"479","author":"Baker","year":"2011","journal-title":"Nature."},{"key":"2019100406463217800_CIT0043","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1172\/JCI64098","article-title":"Cellular senescence and the senescent secretory phenotype: therapeutic opportunities","volume":"123","author":"Tchkonia","year":"2013","journal-title":"J Clin Invest."},{"key":"2019100406463217800_CIT0044","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1111\/acel.12344","article-title":"The Achilles\u2019 heel of senescent cells: from transcriptome to senolytic drugs","volume":"14","author":"Zhu","year":"2015","journal-title":"Aging Cell."},{"key":"2019100406463217800_CIT0045","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1038\/nm.4010","article-title":"Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice","volume":"22","author":"Chang","year":"2016","journal-title":"Nat Med."},{"key":"2019100406463217800_CIT0046","doi-asserted-by":"publisher","first-page":"1392","DOI":"10.1016\/j.leukres.2014.09.016","article-title":"How tyrosine kinase inhibitors impair metabolism and endocrine system function: a systematic updated review","volume":"38","author":"Breccia","year":"2014","journal-title":"Leuk Res."},{"key":"2019100406463217800_CIT0047","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1016\/j.devcel.2014.11.012","article-title":"An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA","volume":"31","author":"Demaria","year":"2014","journal-title":"Dev Cell."},{"key":"2019100406463217800_CIT0048","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1038\/nature03260","article-title":"Rejuvenation of aged progenitor cells by exposure to a young systemic environment","volume":"433","author":"Conboy","year":"2005","journal-title":"Nature."},{"key":"2019100406463217800_CIT0049","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1016\/j.cell.2013.04.015","article-title":"Growth differentiation factor 11 is a circulating factor that reverses age-related cardiac hypertrophy","volume":"153","author":"Loffredo","year":"2013","journal-title":"Cell."},{"key":"2019100406463217800_CIT0050","doi-asserted-by":"publisher","first-page":"152","DOI":"10.18632\/aging.100719","article-title":"Serum from calorie-restricted animals delays senescence and extends the lifespan of normal human fibroblasts in vitro","volume":"7","author":"de Cabo","year":"2015","journal-title":"Aging (Albany NY)."},{"key":"2019100406463217800_CIT0051","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12708","article-title":"Young plasma reverses age-dependent alterations in hepatic function through the restoration of autophagy","volume":"17","author":"Liu","year":"2018","journal-title":"Aging Cell."},{"key":"2019100406463217800_CIT0052","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.12621","article-title":"Exercise-conditioned plasma attenuates nuclear concentrations of DNA methyltransferase 3B in human peripheral blood mononuclear cells","volume":"3","author":"Horsburgh","year":"2015","journal-title":"Physiol Rep."}],"container-title":["The Journals of Gerontology: Series A"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/biomedgerontology\/article-pdf\/74\/11\/1709\/30100717\/gly290.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/biomedgerontology\/article-pdf\/74\/11\/1709\/30100717\/gly290.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,10,4]],"date-time":"2019-10-04T06:47:03Z","timestamp":1570171623000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/biomedgerontology\/article\/74\/11\/1709\/5261449"}},"subtitle":[],"editor":[{"given":"David","family":"Le Couteur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2018,12,26]]},"references-count":52,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2018,12,26]]},"published-print":{"date-parts":[[2019,10,4]]}},"URL":"https:\/\/doi.org\/10.1093\/gerona\/gly290","relation":{},"ISSN":["1079-5006","1758-535X"],"issn-type":[{"value":"1079-5006","type":"print"},{"value":"1758-535X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,11]]},"published":{"date-parts":[[2018,12,26]]}}}