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Journal of Science and Medicine in Sport
Available online 7 September 2026In Press, Journal Pre-proofWhat’s this?
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Author links open overlay panelAyşe Arslan a, Güfat Arslan b
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https://doi.org/10.1016/j.jsams.2026.09.002Get rights and content
Introduction
Overtraining syndrome (OTS) remains one of the least understood conditions in sports medicine. Characterized by persistent performance decline, prolonged fatigue, impaired recovery, and increased susceptibility to infections, OTS develops when cumulative training stress exceeds an athlete's capacity for physiological adaptation.1 A range of mechanisms-including endocrine dysfunction, chronic inflammation, oxidative stress, mitochondrial impairment, and metabolic dysregulation-have been proposed, yet none fully accounts for the sustained immune dysfunction observed in affected athletes or offers a coherent biological explanation.1The concept that immune-cell dysfunction contributes to OTS is not entirely new. More than two decades ago, Urhausen, Gabriel and colleagues proposed that excessive training may impair lymphocyte function and alter cellular immunity, thereby contributing to prolonged recovery and increased susceptibility to infection.2 However, these previous hypotheses were formulated before the current understanding of T-cell exhaustion biology and therefore could not incorporate the molecular and transcriptional programs now known to regulate chronic T-cell dysfunction. Their work, based primarily on changes in lymphocyte subset counts and mitogen-induced proliferation assays, established that intensive training is associated with impaired cellular immune competence, but predates the molecular characterization of exhaustion-specific transcriptional programs (TOX, NR4A) and inhibitory receptor co-expression patterns that define the modern exhaustion phenotype. Accordingly, the present hypothesis should be viewed as a mechanistic extension of these previous concepts rather than a departure from them.
Recent advances in immunology point to a complementary perspective. T-cell exhaustion is now understood as a progressive adaptive program driven by chronic inflammatory and metabolic stress, leading to impaired immune function and reduced cellular adaptability.3., 4., 5. We propose that chronic training overload may induce an exhaustion-like program of T-cell remodeling. Viewed through this lens, OTS may be reframed as an immune remodeling disorder, providing a framework for novel biomarkers and translational research. Support for this concept also comes from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID, where exhaustion-associated T-cell alterations have been reported.6
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