A mathematical model of erythropoiesis suggests an altered plasma volume control as cause for anemia in aged mice

Abstract

In order to evaluate whether the anemia observed in aged C57B1 and B6D2F1 mice reflects a defect in the control mechanisms regulating erythropoiesis a mathematical model of erythropoietic control is employed, validated previously. In the model it is hypothesized that the most important mechanism for compensating an actual demand of red blood cells is an increase in the mitotic amplication (number of mitoses) or erythroid progenitors (CFU-E, erythroblasts). The same sigmoidal dose-response-relationship between mitotic applification and hematocrit (Hct) is proposed for young and aged mice. It is mediated by erythropoietin (EPO). Using this relationship one can demonstrate that the expansion of the plasma volume (PV) observed in aged mice is appropriately compensated by an increase in the mitotic amplification of CFU-E and erythroblasts. This implies that aged mice operate in a stimulated of erythropoietic amplication which is closer to the maximum of the dose-response-relationships than the steady state in young mice. This explains the finding of a reduced proliferative reserve in aged mice following further erythropoietic stimulation. An additional analysis regarding the response of aged mice to bleeding anemia is consistent with the view that young and aged mice share the same dose-response-relationship but start from different steady states. These findings suggest that the control mechanisms regulating erythropoiesis in young and aged mice are similar and that the anemia is due to alterations in the PV control.