{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T13:14:59Z","timestamp":1791206099747,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,11,26]],"date-time":"2014-11-26T00:00:00Z","timestamp":1416960000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG045734"],"award-info":[{"award-number":["AG045734"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["N01-AI-00017"],"award-info":[{"award-number":["N01-AI-00017"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2015,2]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    Aging of the world population and a concomitant increase in age\u2010related diseases and disabilities mandates the search for strategies to increase healthspan, the length of time an individual lives healthy and productively. Due to the age\u2010related decline of the immune system, infectious diseases remain among the top 5\u201310 causes of mortality and morbidity in the elderly, and improving immune function during aging remains an important aspect of healthspan extension. Calorie restriction (\n                    <jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content>\n                    ) and more recently rapamycin (rapa) feeding have both been used to extend lifespan in mice. Preciously few studies have actually investigated the impact of each of these interventions upon\n                    <jats:italic>in vivo<\/jats:italic>\n                    immune defense against relevant microbial challenge in old organisms. We tested how rapa and\n                    <jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content>\n                    each impacted the immune system in adult and old mice. We report that each intervention differentially altered T\u2010cell development in the thymus, peripheral T\u2010cell maintenance, T\u2010cell function and host survival after West Nile virus infection, inducing distinct but deleterious consequences to the aging immune system. We conclude that neither rapa feeding nor\n                    <jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content>\n                    , in the current form\/administration regimen, may be optimal strategies for extending healthy immune function and, with it, lifespan.\n                  <\/jats:p>","DOI":"10.1111\/acel.12280","type":"journal-article","created":{"date-parts":[[2014,11,26]],"date-time":"2014-11-26T06:22:34Z","timestamp":1416982954000},"page":"130-138","source":"Crossref","is-referenced-by-count":96,"title":["Lifespan\u2010extending caloric restriction or m\n                    <scp>TOR<\/scp>\n                    inhibition impair adaptive immunity of old mice by distinct mechanisms"],"prefix":"10.1111","volume":"14","author":[{"given":"Emily L.","family":"Goldberg","sequence":"first","affiliation":[{"name":"Departments of Immunobiology and the Arizona Center on Aging University of Arizona College of Medicine Tucson AZ USA"},{"name":"Department of Nutritional Sciences College of Agriculture and Life Sciences University of Arizona Tucson AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa J.","family":"Romero\u2010Aleshire","sequence":"additional","affiliation":[{"name":"Department of Physiology University of Arizona College of Medicine Tucson AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin R.","family":"Renkema","sequence":"additional","affiliation":[{"name":"Departments of Immunobiology and the Arizona Center on Aging University of Arizona College of Medicine Tucson AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa S.","family":"Ventevogel","sequence":"additional","affiliation":[{"name":"Human Vaccine Institute Duke University Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wade M.","family":"Chew","sequence":"additional","affiliation":[{"name":"Arizona Cancer Center University of Arizona College of Medicine Tucson AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Uhrlaub","sequence":"additional","affiliation":[{"name":"Departments of Immunobiology and the Arizona Center on Aging University of Arizona College of Medicine Tucson AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan J.","family":"Smithey","sequence":"additional","affiliation":[{"name":"Departments of Immunobiology and the Arizona Center on Aging University of Arizona College of Medicine Tucson AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten H.","family":"Limesand","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences College of Agriculture and Life Sciences University of Arizona Tucson AZ USA"},{"name":"Arizona Cancer Center University of Arizona College of Medicine Tucson AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory D.","family":"Sempowski","sequence":"additional","affiliation":[{"name":"Human Vaccine Institute Duke University Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heddwen L.","family":"Brooks","sequence":"additional","affiliation":[{"name":"Department of Physiology University of Arizona College of Medicine Tucson AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janko","family":"Nikolich\u2010\u017dugich","sequence":"additional","affiliation":[{"name":"Departments of Immunobiology and the Arizona Center on Aging University of Arizona College of Medicine Tucson AZ USA"},{"name":"Department of Nutritional Sciences College of Agriculture and Life Sciences University of Arizona Tucson AZ USA"},{"name":"Arizona Cancer Center University of Arizona College of Medicine Tucson AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,11,26]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.9.4.10766"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20090222"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/53A.5.B330"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2010.71"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2012.04.005"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1234"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3945\/jn.110.122408"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/geronj\/46.4.B142"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.02.008"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1172539"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/60.6.688"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3201\/eid1011.040469"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1400188"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2011.00773.x"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08221"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2012.08.013"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11861"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601761"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2007.00345.x"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-013-9572-5"},{"key":"e_1_2_10_22_1","first-page":"3266","article-title":"Tregs 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