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Growing evidence implicates immunosenescence\u2014the age\u2010related decline in immune function\u2014in the onset and persistence of fatigue.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This review synthesizes clinical and experimental data to examine how immunosenescence contributes to ME\/CFS. We focus on chronic inflammation, senescent immune phenotypes, mitochondrial dysfunction, and neuroendocrine imbalance, with emphasis on maladaptive crosstalk among immune, muscular, neuroendocrine, and vascular systems.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Aging immune cells drive chronic inflammation that impairs mitochondrial ATP production and promotes muscle catabolism. Concurrently, HPA\u2010axis suppression and \u03b2\n                      <jats:sub>2<\/jats:sub>\n                      \u2010adrenergic dysfunction amplify immune dysregulation and energy imbalance. Together, these processes illustrate how immunosenescence sustains pathological cross\u2010organ signaling underlying systemic fatigue.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Immunosenescence provides a unifying framework linking immune, metabolic, and neuroendocrine dysfunction in ME\/CFS. Recognizing cross\u2010organ communication highlights its clinical relevance, suggesting biomarkers such as cytokines and exhaustion markers, and supports integrated therapeutic strategies targeting immune and metabolic networks.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cph4.70056","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T07:57:46Z","timestamp":1759132666000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Understanding Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome Physical Fatigue Through the Perspective of Immunosenescence"],"prefix":"10.1002","volume":"15","author":[{"given":"Yingzhe","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Oncology Hospital of Chengdu University of Traditional Chinese Medicine  Chengdu Sichuan 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