Circulating cell-free DNA: an up-coming molecular marker in exercise physiology

Area of Science:

• Exercise Physiology
• Molecular Biology
• Biomedical Science

Background:

• Circulating cell-free DNA (cfDNA) is relevant in exercise physiology and clinical medicine.
• Exercise-induced cfDNA increases may indicate overtraining syndrome and immune function adaptations.
• cfDNA is a model for studying pathophysiological processes in diseases like cancer and autoimmune disorders.

Purpose of the Study:

• To review current knowledge on acute and chronic exercise effects on cfDNA levels.
• To discuss the physiological significance of exercise-induced cfDNA alterations.
• To propose hypotheses regarding cfDNA release mechanisms during and after exercise.

Main Methods:

• Review of existing literature on exercise and cfDNA concentrations.
• Analysis of cfDNA kinetics compared to markers of skeletal muscle damage.
• Investigation of exercise parameters (intensity, duration, energy expenditure) influencing cfDNA levels.

Main Results:

• cfDNA concentrations peak immediately after acute exercise, returning rapidly to baseline.
• cfDNA kinetics differ from delayed markers of skeletal muscle damage (e.g., creatine kinase).
• Exercise intensity, duration, or energy expenditure do not fully explain cfDNA increases; complex physiological stress is implicated.

Conclusions:

• Acute exercise likely involves rapid, yet unknown, active or passive cfDNA release mechanisms, possibly involving immune cell activation (e.g., NETosis).
• Chronic high-intensity exercise can lead to persistent cfDNA increases, potentially due to chronic inflammation and cell death (apoptosis/necrosis).
• The role of cfDNA as a marker for overtraining, performance, or exhaustion remains unclear, necessitating longitudinal studies with standardized methods.