Short-term intensive fasting improves red blood cell function and rejuvenates erythropoiesis via regulating MS4A3-CDK2 module

Abstract

Fasting is known to improve health, but the precisely beneficial effects of specific types of fasting and their underlying mechanisms are not fully understood. We herein report that in humans, occasional short-term intensive fasting (STIF), a traditional fasting format favored by Asians, promotes erythropoiesis and boosts the function of red blood cells (RBCs) in oxygen transportation, ATP generation, antioxidant capacity, and innate immune response. The rejuvenation of erythropoiesis is more pronounced in humans with low RBC counts. Using mouse models and a human erythroid progenitor cell model, we found that occasional STIF rejuvenates erythropoiesis by enhancing megakaryocyte-erythroid progenitor selfrenewal and erythroid-biased differentiation without compromising normal hematopoiesis. Molecularly, STIF relies on an autophagy-dependent but erythropoietin (EPO) upregulation-independent MS4A3-CDK2 module to augment the production of RBCs. Our findings thus suggest that STIF can occasionally be practiced as an efficient noninvasive intervention for better erythropoiesis, particularly for adults with low RBC counts.

Physiological and Psychological Effects of Medically Supervised Fasting in Young Female Adults: An Observational Study

“…A recent study on seven days of water-only fasting also reported an increase in RBC levels and hemoglobin. They also reported that the increase in RBC levels is independent of RBC apoptosis, suggesting an upregulation of hematopoietic systems [ 31 ].…”