Fig. 7: The origin of neocytolysis.

a The organism responds to lower oxygen availability at high altitudes by increasing the concentration of EPO. Within our paradigm, this would lengthen the lifespan of circulating RBCs (1), reducing their rate of destruction and contributing to increase the number of cells in the blood. New RBCs formed in these conditions would also exhibit longer predefined lifespans (2). b Returning to sea level would entail a drop in the concentration of EPO. According to our model, this would reduce RBC lifespan (3 and 4) and cause the formation of short-lived RBCs (5). Therefore, cohorts of RBCs that differ in their expected lifespan would coexist in the blood. c A sharp decrease in EPO levels could cause the destruction of RBCs through the immune phagocytosis, triggering an anti-RBC response, which would further reduce the lifespan of circulating cells. d The reduction in lifespan caused by the return to normal oxygen levels entails the instantaneous destruction of RBCs that have reached a critical age. This age threshold is not absolute but relative to each cohort of RBCs depending on their expected lifespan. Short-lived die when their expected lifespan falls from L₁ to \({L}_{1}^{{\prime} }\) (1) whereas long-lived RBCs of the same age continue to circulate in the blood (2).