Pathophysiological mechanisms of fatigue and multidisciplinary management strategies (Review)

Feb 16, 2026Experimental and therapeutic medicine

Causes of fatigue and combined treatment approaches

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Abstract

Fatigue is associated with complex interactions among energy metabolism, neuroendocrine, and immune systems.

Fatigue involves multilevel regulation of various physiological systems.
Abnormal energy metabolism, oxidative stress, and mitochondrial dysfunction are key factors in the development of fatigue.
Disruptions in the neuro-endocrine-immune network and the microbiome-gut-brain axis play significant roles in fatigue mechanisms.
Fatigue symptoms can arise from various clinical conditions, including chronic fatigue syndrome and several endocrine, neurological, and autoimmune disorders.
Individualized, multidisciplinary care models are recommended for effective fatigue management.
Telemedicine has improved accessibility and adherence to fatigue management strategies.

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Fatigue is a common clinical symptom, and its complex pathophysiological mechanisms markedly affect the quality of life and social function of patients. With the advancement of omics technologies and artificial intelligence applications, the ability to understand the mechanisms of fatigue has been notably enhanced. Fatigue is a complex process involving the interaction of multiple systems and factors. The occurrence of fatigue involves multilevel regulation of energy metabolism, neuroendocrine and immune systems. Based on omics and molecular biology, abnormal energy metabolism, oxidative stress and mitochondrial dysfunction serve a central role in the pathogenesis of fatigue. Disorders in the neuro-endocrine-immune network and dysfunction of the microbiome-gut-brain axis constitute key systemic integration mechanisms. Clinically, numerous diseases, including chronic fatigue syndrome and endocrine, neurological and autoimmune disease, can manifest as fatigue symptoms. In terms of treatment, individualized, multidisciplinary collaborative comprehensive management models have become nursing standards. In addition, the application of telemedicine technology has markedly improved the accessibility and compliance of fatigue management. The present review aimed to examine the conceptual framework, physiological mechanisms, clinical manifestations and management strategies of fatigue to provide reference for clinical diagnosis and treatment practice. Future research should focus on strengthening the exploration and translational application of molecular mechanisms, developing novel intervention targets, establishing effective fatigue assessment models and optimizing management strategies to provide strong evidence-based support for clinical practice.

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Pathophysiological mechanisms of fatigue and multidisciplinary management strategies (Review)

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