Red blood cells have a hidden backup route for making hemoglobin
When the blood-making system comes under pressure, the body has a fallback plan. Researchers have discovered an entirely unknown pathway that allows red blood cells to acquire the building blocks for hemoglobin…
Hemoglobin is the protein that carries oxygen through the body. To make it, developing red blood cells need heme — an iron-containing molecular component. Until now, the prevailing view was that red blood cells synthesize heme internally as they mature in the bone marrow. A study published in Science overturns part of that picture: red blood cells can also import heme from surrounding cells through a previously undescribed mechanism.
This so-called cell-nonautonomous heme acquisition pathway turned out to be most active under stress — when the body urgently needs to produce large numbers of new red blood cells, such as after blood loss or during hemolytic anemia, a condition where red blood cells are destroyed faster than they can be replaced. In these situations, internal heme synthesis cannot keep pace. The newly discovered route compensates for that shortfall.
A safety net hiding in plain sight
The mechanism was not invented — it was already there, simply undetected. The researchers used mouse models and cell culture experiments to map the pathway. They identified specific transport proteins responsible for transferring heme between cells, and found that these proteins are upregulated precisely when red blood cell production — a process called erythropoiesis — is under strain.
For patients with chronic anemia, sickle cell disease, or thalassemia — inherited blood disorders that disrupt hemoglobin production — this pathway could represent a new therapeutic target. If the backup route can be pharmacologically activated or enhanced, it might improve oxygen delivery in patients who currently have limited treatment options short of bone marrow transplantation.
Aging and the anemia connection
There is a direct link to aging here. Anemia becomes significantly more common with age and is associated with fatigue, cognitive decline, increased fall risk, and higher mortality. Roughly a third of adults over 65 have some form of anemia. A substantial fraction of those cases have no clearly identifiable cause — a condition known as unexplained anemia of aging. Whether a declining capacity in this heme acquisition mechanism contributes to that pattern remains unknown.
The study does not answer that question directly, but it raises it. What the research does establish is that the biology of red blood cell development is more intricate than previously thought — and that therapeutic angles exist which, until now, were not even on the map.