Red blood cells, or erythrocytes, are the most numerous cell type in human blood. Their primary role is to transport oxygen from the lungs to the body’s tissues. They accomplish this using a specialized protein called hemoglobin, which binds to oxygen molecules. The life of a healthy red blood cell is a finite journey, lasting on average about 120 days.
Red Blood Cell Production
The creation of new red blood cells is a process known as erythropoiesis. This process primarily takes place within the red bone marrow, the soft tissue inside bones like the vertebrae, ribs, and pelvis in adults. The entire process is regulated by a hormone called erythropoietin, or EPO. When oxygen levels in the blood decrease, specialized cells in the kidneys detect this change and increase their production of EPO.
EPO travels through the bloodstream to the bone marrow, where it signals hematopoietic stem cells to begin differentiating into red blood cells. During maturation, the precursor cell, called an erythroblast, undergoes significant changes. It synthesizes large amounts of hemoglobin and, in a final step, ejects its nucleus and other internal structures like mitochondria. This results in a flexible, biconcave disc known as a reticulocyte, which enters circulation and becomes a fully mature erythrocyte within a day or two.
Function and Aging in Circulation
Once in the bloodstream, the mature red blood cell’s existence is dedicated to oxygen transport. Its biconcave shape provides a large surface area for efficient gas exchange, and its flexibility is important. This deformability allows the 7-micrometer cell to squeeze through the narrowest capillaries, some of which are only 2-3 micrometers in diameter, to deliver oxygen directly to tissues. This constant travel, however, subjects the cell to mechanical and shear stress.
Because the mature erythrocyte lacks a nucleus, it contains no DNA and cannot synthesize new proteins to repair damage. The squeezing through capillaries and exposure to oxidative stress gradually damages its cell membrane. Over time, the cell becomes less flexible and its membrane properties change, signaling that it is nearing the end of its functional life.
Clearance and Recycling
At the end of their lifespan, old or damaged red blood cells are removed from circulation by specialized immune cells called macrophages. While this process occurs in the spleen, liver, and bone marrow, recent studies indicate the liver is a major site for clearing damaged cells on demand. Macrophages in these organs recognize signals on the surface of aging erythrocytes and engulf them in a process called phagocytosis. This prevents the old cells from breaking down in the bloodstream, which would release toxic levels of hemoglobin and iron.
This system efficiently recycles valuable components. Once a macrophage consumes an old red blood cell, it breaks down the hemoglobin molecule. The iron atom at the core of the heme group is recovered. This iron is then bound to a transport protein and carried back to the bone marrow, where it is used to produce hemoglobin for a new generation of erythrocytes. The remainder of the heme molecule is converted into other compounds, which are processed by the liver and eventually excreted from the body.