{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T06:55:21Z","timestamp":1778050521451,"version":"3.51.4"},"reference-count":77,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2019,7,29]],"date-time":"2019-07-29T00:00:00Z","timestamp":1564358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"The Glenn Medical Foundation"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AG022303"],"award-info":[{"award-number":["AG022303"]}],"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":["AG024824"],"award-info":[{"award-number":["AG024824"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Research Training in Experimental Immunology Training Grant","award":["T32-AI007413"],"award-info":[{"award-number":["T32-AI007413"]}]},{"name":"Career Training in the Biology of Aging Training Grant","award":["T32-AG000114"],"award-info":[{"award-number":["T32-AG000114"]}]},{"name":"Geriatrics Research, Education and Clinical Care Center"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The National Institute on Aging (NIA)-sponsored Interventions Testing Program (ITP) has identified a number of dietary drug interventions that significantly extend life span, including rapamycin, acarbose, and 17-\u03b1 estradiol. However, these drugs have diverse downstream targets, and their effects on age-associated organ-specific changes are unclear (Nadon NL, Strong R, Miller RA, Harrison DE. NIA Interventions Testing Program: investigating putative aging intervention agents in a genetically heterogeneous mouse model. EBioMedicine. 2017;21:3\u20134. doi:10.1016\/j.ebiom.2016.11.038). Potential mechanisms by which these drugs extend life could be through their effect on inflammatory processes often noted in tissues of aging mice and humans. Our study focuses on the effects of three drugs in the ITP on inflammation in gonadal white adipose tissue (gWAT) of HET3 mice\u2014including adiposity, adipose tissue macrophage (ATM) M1\/M2 polarization, markers of cellular senescence, and endoplasmic reticulum stress. We found that rapamycin led to a 56% increase of CD45+ leukocytes in gWAT, where the majority of these are ATMs. Interestingly, rapamycin led to a 217% and 106% increase of M1 (CD45+CD64+CD206\u2212) ATMs in females and males, respectively. Our data suggest rapamycin may achieve life-span extension in part through adipose tissue inflammation. Additionally, HET3 mice exhibit a spectrum of age-associated changes in the gWAT, but acarbose and 17-\u03b1 estradiol do not strongly alter these phenotypes\u2014suggesting that acarbose and 17- \u03b1 estradiol may not influence life span through mechanisms involving adipose tissue inflammation.<\/jats:p>","DOI":"10.1093\/gerona\/glz177","type":"journal-article","created":{"date-parts":[[2019,7,29]],"date-time":"2019-07-29T00:30:18Z","timestamp":1564360218000},"page":"89-98","source":"Crossref","is-referenced-by-count":23,"title":["Life-span Extension Drug Interventions Affect Adipose Tissue Inflammation in Aging"],"prefix":"10.1093","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4278-6438","authenticated-orcid":false,"given":"Theresa","family":"Mau","sequence":"first","affiliation":[{"name":"Division of Geriatric and Palliative Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor"},{"name":"Graduate Program in Immunology, Program in Biomedical Sciences (PIBS), University of Michigan, Ann Arbor"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"Division of Geriatric and Palliative Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amiya K","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Division of Geriatric and Palliative Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard A","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Pathology and Glenn Center for Biology of Aging Research, University of Michigan, Ann Arbor"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raymond","family":"Yung","sequence":"additional","affiliation":[{"name":"Division of Geriatric and Palliative Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor"},{"name":"Graduate Program in Immunology, Program in Biomedical Sciences (PIBS), University of Michigan, Ann Arbor"},{"name":"Department of Pathology and Glenn Center for Biology of Aging Research, University of Michigan, Ann Arbor"},{"name":"Geriatric Research, Education, and Clinical Care Center (GRECC), VA Ann Arbor Health System, Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,7,29]]},"reference":[{"key":"2019121307581542500_CIT0001","doi-asserted-by":"publisher","first-page":"2375","DOI":"10.1002\/eji.1830230950","article-title":"Increased cytokine production in mononuclear cells of healthy elderly people","volume":"23","author":"Fagiolo","year":"1993","journal-title":"Eur J 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