{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T13:15:11Z","timestamp":1780578911064,"version":"3.54.1"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Aging is associated with impaired T cell immune responses, raising the susceptibility of the elderly to infections and cancers. Aged T cells exhibit impaired T cell responses to T cell receptor (TCR) stimulation accompanied by reduced glycolytic activity, but the molecular basis of these defects is largely elusive. Using data-independent acquisition (DIA) mass spectrometry-based proteomic analysis, we identified pyruvate dehydrogenase kinase 1 (PDHK1), a key glycolytic enzyme, as significantly downregulated in aged murine T cells. This loss of PDHK1 expression was confirmed in both CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells from aged mice, regardless of their na\u00efve or activated state. Consistent with this, aged T cells exhibited defects in the activation of glycolysis immediately after TCR stimulation. Furthermore, CRISPR-mediated\n                    <jats:italic>Pdhk1<\/jats:italic>\n                    deletion in young T cells led to defective activation and effector molecule expression upon TCR stimulation, whereas enforced PDHK1 expression in aged T cells facilitated these responses. These data suggest that aging diminishes PDHK1 expression in T cells, contributing to impaired glycolysis and T cell responses, which can be therapeutically restored by PDHK1 overexpression.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1800870","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T14:50:00Z","timestamp":1778511000000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Age-related reduction of pyruvate dehydrogenase kinase 1 impairs T cell responses"],"prefix":"10.3389","volume":"17","author":[{"given":"Rajkumar S.","family":"Kalra","sequence":"first","affiliation":[{"name":"Immune Signal Unit, Okinawa Institute of Science and Technology, Graduate University (OIST)","place":["Onna-son, Okinawa, Japan"]},{"name":"Department of Molecular Biosciences, Radiation Effects Research Foundation","place":["Hiroshima, 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