Intermittent Caloric Restriction Promotes Erythroid Development and Ameliorates Phenylhydrazine-Induced Anemia in Mice

BACKGROUND: Dietary restriction has a profound effect in altering immune system and promoting metabolic health and aging. However, how dietary restriction impacts erythroid system is largely unknown. We found that a short-term caloric restriction (CR) stimulates expression of KLF1, a master regulator of erythroid development, in the spleen of mouse, and thus explored the potential effect of CR on erythropoiesis. METHODS: We analyzed the effects of intermittent CR and continuous CR for different lengths of time on parameters of peripheral blood and erythroid profiles in the spleen and bone marrow in C57BL/6 mice. We next assessed how different types of CR affect phenylhydrazine-induced anemia in the mice. Colony formation assay was also used to analyze LK + progenitors and BFU-E in the bone marrow. RESULTS: Intermittent CR for 2 weeks raised the number of reticulocytes in the blood, while continuous CR for 2 weeks elevated red blood cells and hemoglobin level. Intermittent CR for 2 weeks promoted extramedullary hematopoiesis in the spleen, while continuous CR mainly promoted erythropoiesis in the bone marrow. Interestingly, a short-term intermittent CR but not continuous CR was able to ameliorate phenylhydrazine-induced anemia. Intermittent CR reduced early-stage erythroblasts and increased late-stage erythroblasts/mature RBCs in the spleen, indicating an accelerated transition from early-stage to late-stage erythroblasts/mature red blood cells. Furthermore, a short-term intermittent CR elevated LK + progenitors and the committed erythroid progenitor cells BFU-E in the bone marrow. CONCLUSION: Our study demonstrated that a short-term intermittent CR, but not continuous CR, has a significant effect to promote hematopoiesis and such activity can ameliorate phenylhydrazine-induced acute anemia in the mouse.