Long-Distance Trail Running Induces Inflammatory-Associated Protein, Lipid, and Purine Oxidation in Red Blood Cells

Area of Science:

• Exercise Physiology
• Red Blood Cell Biology
• Molecular Omics

Background:

• Ultra-endurance running places significant stress on oxygen transport systems.
• The molecular responses of red blood cells (RBCs) to extreme exercise are not well understood.

Purpose of the Study:

• To investigate the molecular and functional adaptations of RBCs in response to different durations of ultra-endurance running.
• To identify biomarkers associated with exercise-induced RBC damage and aging.

Main Methods:

• Integrated plasma and RBC multi-omics (proteomics, metabolomics) with hematology and hemorheology.
• Analyzed athlete samples before and after a 40-km marathon (MCC) and a 171-km ultramarathon (UTMB).
• Assessed systemic inflammation markers, RBC metabolic pathways, protein oxidation, and rheological properties.

Main Results:

• Both races induced inflammation; the UTMB showed higher IL-6, kynurenine, and lipid remodeling.
• RBCs exhibited altered metabolism (Lands cycle, purine salvage) and non-random protein oxidation, particularly of antioxidant enzymes.
• Impaired RBC deformability correlated with protein oxidation and elevated copper, suggesting accelerated RBC aging beyond mechanical stress.

Conclusions:

• Ultra-running accelerates RBC aging through inflammatory and oxidative pathways, impacting RBC biomechanics and leading to splenic sequestration.
• Identified novel biomarkers for exercise-induced hemolysis and provided insights into RBC oxidative damage relevant to transfusion and inflammatory diseases.