| Summary: | Our knowledge on the molecular mechanisms of red blood cell aging is mostly derived from in vitro studies. The Four Days Marches of Nijmegen in the Netherlands, the world’s largest yearly walking event, constitutes a unique possibility to study the effect of mechanical and biochemical stressors occurring during moderate-intensity exercise on red blood cell aging in vivo. Therefore, longitudinal measurements were performed of biophysical, immunological, and functional red blood cell characteristics that are known to change during aging. Our data show that moderate-intensity exercise induces the generation of a functionally improved red blood cell population with a higher deformability and a decreased tendency to aggregate. This is likely to be associated with an early removal of the oldest red blood cells from the circulation, as deduced from the (dis)appearance of removal signals. Thus, the physiological red blood cell aging process maintains homeostasis in times of moderate-intensity exercise-induced stress, probably by accelerated aging and subsequent removal of the oldest, most vulnerable red blood cells.
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