Xu et al. (2026)
- Authors: Huimin Xu, Yingzhe Luo, Xi Wu, Shaoquan Xiong, Jianlong Ke
- Institutes: School of Health and Life Sciences, Chengdu University, Chengdu, China
- Publisher: Comprehensive Physiology (Wiley)
- Link: DOI
Summary
This research proposes a new ‘immune-vascular-cognitive axis’ to explain the biological roots of ‘brain fog’ in ME/CFS. By linking the premature aging of the immune system to the breakdown of blood flow regulation in the brain, it provides a unifying theory for how peripheral inflammation leads to central neurological symptoms. This framework shifts the focus toward integrated treatments that address immune health and vascular function simultaneously to restore cognitive energy.
What was researched?
The study investigates how immunosenescence—the stress-related deterioration of immune system function—drives blood flow dysregulation and cognitive impairment in ME/CFS patients.
Why was it researched?
Researchers sought to create a unifying framework for ‘brain fog’ and fatigue, symptoms that are often studied in isolation but likely share a common origin in the crosstalk between the immune and vascular systems.
How was it researched?
The authors conducted an integrative review of clinical and experimental data, examining the role of ‘inflammaging,’ senescent immune cell phenotypes (T, B, and NK cells), and their impact on the vascular system.
What has been found?
The study found that immune aging promotes chronic low-grade inflammation that impairs endothelial nitric oxide 💊 production and damages the blood-brain barrier. This leads to brain hypoperfusion and oxidative stress, which starves the brain of energy (ATP) and disrupts the neural networks essential for memory and focus.
Discussion
The proposed model suggests that cognitive dysfunction in ME/CFS is a downstream effect of peripheral immune exhaustion and endothelial senescence. While the model is supported by existing data, the authors emphasize the need for more integrated studies that measure these systems concurrently in patient cohorts.
Conclusion & Future Work
The review concludes that immunosenescence is a key driver of ME/CFS pathology and suggests that therapies targeting mitochondrial health and vascular restoration could offer new ways to treat the disease.