Nunes et al. (2026)
- Authors: Massimo Nunes, Loren Kell, Anouk Slaghekke, Rob C. I. Wüst, Burtram C. Fielding, Douglas B. Kell, Etheresia Pretorius
- Institutes: Department of Physiological Sciences, Stellenbosch University, Stellenbosch, South Africa, Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands, Department of Medical Biosciences, University of the Western Cape, Bellville, South Africa, Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
- Publisher: Cell Death & Disease
- Link: DOI
Summary
This research introduces a groundbreaking perspective by identifying endothelial senescence as the possible missing link in ME/CFS and Long COVID. By explaining why symptoms persist long after a virus is gone, it offers a clear biological target for diagnostic tests and potential cures. This shift in focus from broad inflammation to specific zombie cells in the vascular system provides hope for more effective, targeted medical interventions.
What was researched?
This study proposes a new theoretical framework where virus-induced endothelial senescence acts as a primary driver for ME/CFS and Long COVID. It explores how a dysfunctional immune system fails to clear these damaged blood vessel cells, leading to chronic illness.
Why was it researched?
Despite the overlapping symptoms of ME/CFS and Long COVID, a clear mechanistic explanation for why these diseases persist has been missing. This research aims to provide a unifying biological model to help identify biomarkers and develop targeted treatments.
How was it researched?
The authors conducted a comprehensive synthesis of literature on endothelial dysfunction, cellular senescence, and immune responses in post-viral conditions. They analyzed the impact of the Senescence-Associated Secretory Phenotype (SASP) on blood flow, inflammation, and tissue repair across various organ systems.
What has been found?
The paper identifies that viral infections can cause endothelial cells to enter a senescent state, releasing harmful factors that promote inflammation and blood clotting while restricting blood flow. In healthy individuals, the immune system removes these cells, but in ME/CFS and Long COVID patients, immune abnormalities appear to prevent this clearance. This failure results in a self-sustaining cycle of damaged cells that impair oxygen delivery to vital organs.
Discussion
A major strength of this model is its ability to explain diverse symptoms like post-exertional malaise and brain fog through impaired regional blood flow. However, as a theoretical paper, these proposed mechanisms require further empirical validation in clinical cohorts using specific senescent cell markers.
Conclusion & Future Work
The authors conclude that recognizing endothelial senescence as a central feature of these diseases is vital for clinical progress. They suggest that future research should investigate methods to clear senescent cells or neutralize their harmful secretions to restore vascular health.