{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:31:39Z","timestamp":1792042299833,"version":"4.4.0"},"reference-count":50,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T00:00:00Z","timestamp":1747785600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T00:00:00Z","timestamp":1747785600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100011701","name":"British Society for Research on Ageing","doi-asserted-by":"publisher","award":["REF\u2010SRG23\u201001"],"award-info":[{"award-number":["REF\u2010SRG23\u201001"]}],"id":[{"id":"10.13039\/100011701","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    T\u2010cell metabolism is a key regulator of immune function. Metabolic dysfunction in T cells from young mice results in an aged phenotype, accelerating immunosenescence. Physical activity (PA) maintains T\u2010cell function and delays immunosenescence in older adults, but the underlying mechanisms are poorly understood. We investigated the effects of PA on the metabolic and functional profiles at a single\u2010cell resolution of resting and stimulated T cells from young adults (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u20099, 23\u2009\u00b1\u20093\u2009years) and physically active older adults clustered between higher PA (HPA,\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u20099, 75.5\u2009\u00b1\u20094.7\u2009years) or lower PA levels (LPA,\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u200910, 76.4\u2009\u00b1\u20092.1\u2009years). Compared to young donors, HPA older adults had higher mitochondrial dependence (MD) and lower glucose dependence (GD) in unstimulated na\u00efve, central memory (CM) and effector memory (EM) CD4\n                    <jats:sup>+<\/jats:sup>\n                    and EM CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, while LPA older adults had higher overall protein synthesis in na\u00efve and EM CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    . In response to PMA and Ionomycin stimulation, there was a similar increase in GD and a reduction in MD across groups for most T\u2010cell subsets. Although LPA and HPA underwent a higher increase in protein synthesis upon activation compared to the young subjects, HPA did not exhibit the excessive increase in the percentage of IL\u20106\n                    <jats:sup>+<\/jats:sup>\n                    T cells observed in the LPA group compared to young subjects. Taken together, our data provide evidence of a higher energy demand, impaired metabolic flexibility, and hyperinflammatory responses in aged T cells, and PA reduces metabolic demand in these cells, potentially through increased MD and improved metabolic flexibility.\n                  <\/jats:p>","DOI":"10.1111\/acel.70104","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T01:38:47Z","timestamp":1747877927000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Physical Activity Modifies the Metabolic Profile of\n                    <scp>CD4<\/scp>\n                    <sup>+<\/sup>\n                    and\n                    <scp>CD8<\/scp>\n                    <sup>+<\/sup>\n                    T\u2010Cell Subtypes at Rest and Upon Activation in Older Adults"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4280-4889","authenticated-orcid":false,"given":"Jon","family":"Hazeldine","sequence":"first","affiliation":[{"name":"Department of Inflammation and Aging University of Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Withnall","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Aging University of Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alba","family":"Llibre","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Aging University of Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niharika A.","family":"Duggal","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Aging University of Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1030-6786","authenticated-orcid":false,"given":"Janet M.","family":"Lord","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Aging University of Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0575-7996","authenticated-orcid":false,"given":"Amanda V.","family":"Sardeli","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Aging University of Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,21]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2016.09.002"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.57950"},{"key":"e_1_2_7_4_1","article-title":"High\u2010Intensity Interval Training Increases Rheumatoid Arthritis Cardiorespiratory Fitness in Association With Improvements in CD4+ T Cell and Skeletal Muscle Mitochondrial Metabolism","volume":"72","author":"Andonian B.","year":"2020","journal-title":"ACR Convergence"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.11.007"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.102438"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12675"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fragi.2021.681428"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2020.03.016"},{"key":"e_1_2_7_10_1","first-page":"911","article-title":"Age\u2010Related Increase of Mitochondrial Content in Human Memory CD4+ T Cells Contributes to ROS\u2010Mediated Increased Expression of Proinflammatory Cytokines","volume":"13","author":"Chen Y.","year":"2022","journal-title":"Frontiers in Immunology"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aax0860"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-061020-053702"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0177-9"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12750"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749\u20106632.2000.tb06651.x"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2010.03.003"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1249\/MSS.0b013e318213fefb"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1249\/MSS.0000000000003483"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD010596.pub3"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fragi.2020.602108"},{"key":"e_1_2_7_21_1","first-page":"54","article-title":"A Scoping Review on the Effects of Physical Exercise and Fitness on Peripheral Leukocyte Energy Metabolism in Humans","volume":"29","author":"Hodgman C. 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