Physiological and pathophysiological significance of erythrocyte senescence, density and deformability: Important but unnoticed trinity

Erythrocytes are the most abundant cells and acting as carrier, deliverer and sensor of oxygen. Therefore, human erythrocyte behavior is a fundamental health indicator. Lifespan of circulating erythrocytes is about 120 days, and hence erythrocyte population shows distribution of aging. The physicochemical property of hemoglobin (Hb) influences the density and the deformability of erythrocytes. Senescent erythrocytes are dense, shrunk, less deformable and finally removed from circulation by several mechanisms such as phagocytosis and eryptosis. Earlier removal leads to the short lifespan of less deformable erythrocytes. Herein, anemic and cardiometabolic diseases are presented in order to consider the relationship between the agedependent erythrocyte density and deformability. The main cause of impaired deformability in sickle cell disease is the presence of dense cells characterized by cellular dehydration and polymerization of sickle Hb, that in hereditary hemolytic diseases is cellular geometry, and that in iron deficiency anemia is an increased susceptibility of lighter erythrocytes to the oxidative stress. Diabetic erythrocytes show seemingly normal density and reduced deformability under the enhanced oxidative stress. This article addresses that distribution profiles of both erythrocyte density and deformability are important for better understanding of the encapsulated Hb interacting membrane of erythrocytes showing individual aging.