Unravelling the Connection Between Energy Metabolism and Immune Senescence/Exhaustion in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating disease, characterized by a diverse array of symptoms including post-exertional malaise (PEM), severe fatigue, and cognitive impairments, all of which drastically diminish the patients’ quality of life. Despite its impact,...

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Main Authors: Jente Van Campenhout, Yanthe Buntinx, Huan-Yu Xiong, Arne Wyns, Andrea Polli, Jo Nijs, Joeri L. Aerts, Thessa Laeremans, Jolien Hendrix
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Biomolecules
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Online Access:https://www.mdpi.com/2218-273X/15/3/357
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author Jente Van Campenhout
Yanthe Buntinx
Huan-Yu Xiong
Arne Wyns
Andrea Polli
Jo Nijs
Joeri L. Aerts
Thessa Laeremans
Jolien Hendrix
author_facet Jente Van Campenhout
Yanthe Buntinx
Huan-Yu Xiong
Arne Wyns
Andrea Polli
Jo Nijs
Joeri L. Aerts
Thessa Laeremans
Jolien Hendrix
author_sort Jente Van Campenhout
collection DOAJ
description Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating disease, characterized by a diverse array of symptoms including post-exertional malaise (PEM), severe fatigue, and cognitive impairments, all of which drastically diminish the patients’ quality of life. Despite its impact, no curative treatments exist, largely due to the limited understanding of the disease’s underlying pathophysiology. Mitochondrial dysfunction, leading to impaired energy production and utilization, is believed to play a key role in the onset of fatigue and PEM, positioning it as a potential key pathophysiological mechanism underlying ME/CFS. Additionally, the disorder shows similarities to chronic viral infections, with frequent reports of immune system alterations, suggesting a critical role for immune (dys)functioning. In particular, the roles of immune senescence and immune exhaustion—two fundamental immune states—remain poorly understood in ME/CFS. This state-of-the-art review explores how metabolic dysfunction and immune dysfunction may be interconnected in ME/CFS, proposing that energy deficits may directly impair immune function. By examining this metabolic–immune interplay, this review highlights potential pathways for developing innovative therapeutic strategies that target both energy metabolism and immune regulation, offering hope for improving patient outcomes.
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spelling doaj-art-74f6ea2f2db14d06aaa1e6e39881be5a2025-08-20T03:43:30ZengMDPI AGBiomolecules2218-273X2025-03-0115335710.3390/biom15030357Unravelling the Connection Between Energy Metabolism and Immune Senescence/Exhaustion in Patients with Myalgic Encephalomyelitis/Chronic Fatigue SyndromeJente Van Campenhout0Yanthe Buntinx1Huan-Yu Xiong2Arne Wyns3Andrea Polli4Jo Nijs5Joeri L. Aerts6Thessa Laeremans7Jolien Hendrix8Pain in Motion Research Group (PAIN), Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, BelgiumPain in Motion Research Group (PAIN), Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, BelgiumPain in Motion Research Group (PAIN), Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, BelgiumPain in Motion Research Group (PAIN), Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, BelgiumPain in Motion Research Group (PAIN), Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, BelgiumPain in Motion Research Group (PAIN), Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, BelgiumLaboratory of Neuro-Aging & Viro-Immunotherapy, Center for Neurosciences, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, BelgiumLaboratory of Neuro-Aging & Viro-Immunotherapy, Center for Neurosciences, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, BelgiumPain in Motion Research Group (PAIN), Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, BelgiumMyalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating disease, characterized by a diverse array of symptoms including post-exertional malaise (PEM), severe fatigue, and cognitive impairments, all of which drastically diminish the patients’ quality of life. Despite its impact, no curative treatments exist, largely due to the limited understanding of the disease’s underlying pathophysiology. Mitochondrial dysfunction, leading to impaired energy production and utilization, is believed to play a key role in the onset of fatigue and PEM, positioning it as a potential key pathophysiological mechanism underlying ME/CFS. Additionally, the disorder shows similarities to chronic viral infections, with frequent reports of immune system alterations, suggesting a critical role for immune (dys)functioning. In particular, the roles of immune senescence and immune exhaustion—two fundamental immune states—remain poorly understood in ME/CFS. This state-of-the-art review explores how metabolic dysfunction and immune dysfunction may be interconnected in ME/CFS, proposing that energy deficits may directly impair immune function. By examining this metabolic–immune interplay, this review highlights potential pathways for developing innovative therapeutic strategies that target both energy metabolism and immune regulation, offering hope for improving patient outcomes.https://www.mdpi.com/2218-273X/15/3/357mitochondrial dysfunctionbiomarkernatural killer cellcytotoxic T cellfatiguepain
spellingShingle Jente Van Campenhout
Yanthe Buntinx
Huan-Yu Xiong
Arne Wyns
Andrea Polli
Jo Nijs
Joeri L. Aerts
Thessa Laeremans
Jolien Hendrix
Unravelling the Connection Between Energy Metabolism and Immune Senescence/Exhaustion in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Biomolecules
mitochondrial dysfunction
biomarker
natural killer cell
cytotoxic T cell
fatigue
pain
title Unravelling the Connection Between Energy Metabolism and Immune Senescence/Exhaustion in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
title_full Unravelling the Connection Between Energy Metabolism and Immune Senescence/Exhaustion in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
title_fullStr Unravelling the Connection Between Energy Metabolism and Immune Senescence/Exhaustion in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
title_full_unstemmed Unravelling the Connection Between Energy Metabolism and Immune Senescence/Exhaustion in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
title_short Unravelling the Connection Between Energy Metabolism and Immune Senescence/Exhaustion in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
title_sort unravelling the connection between energy metabolism and immune senescence exhaustion in patients with myalgic encephalomyelitis chronic fatigue syndrome
topic mitochondrial dysfunction
biomarker
natural killer cell
cytotoxic T cell
fatigue
pain
url https://www.mdpi.com/2218-273X/15/3/357
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