Editorial board editor-in-chief

The role of clock machinery in 
programmed erythrocyte death
The mechanism of aging and dying in nucleated cells is believed 
to be hidden in the mechanism for telomere length regulation. 
It must be a different mechanism in case of erythrocytes. The 
cell membrane is a determinant of life span. Turnover in living 
organisms and storage of erythrocyte concentrate are associ-
ated with gradual loss of membrane fragments [26]. Biologically 
determined less stable fragments of phospholipid membrane are 
probably lost [27]. The process is more pronounced in an acid 
milieu and at elevated (tissue) temperature [28]. This in turn 
reduces surface area for gas exchange and leads to the loss of 
proteins anchored in microvesicles shed by erythrocytes. The 
process decreases also the ability of red blood cells to deform. 
It is associated with the increased internal viscosity of the eryth-
rocyte and alterations in red blood cell membrane properties. 
For this reason the return to its original shape during passage 
through tissues is slower than usually. Red blood cells become 
spherical. The increased viscosity of old blood cells has been 
used for separation of cells [29, 30].
After the erythrocyte has passed through the vascular system 
a given number of times, it is not able to undergo a certain set 
of indispensable metabolic rearrangements in its sojourn in the 
lung or peripheral tissues.
Repeated reduction in red cell surface area and volume 
reaches the limit beyond which the trigger process is initiated 
to induce changes in the structure of the erythrocyte. It serves 
as one of the signals that allow macrophages to recognise aged 
cells. With the loss of cell membrane integrity, erythrocytes also 
loose various substances that protect them from being rec-
ognized by the reticuloendothelial system in the liver and the 
spleen. The formation of microvesicles with low protein content 
favors the increase in concentration of certain proteins in the 
membrane and increases the risk of their aggregation. Such 
protein conglomerates may bind immunoglobulins, which is an 
additional signal for phagocytes. Evidence shows that the number 
of immunoglobulin-coated erythrocytes increases with advancing 
age [31]. However, it does not appear to be the fundamental 
mechanism for recognizing old cells – erythrocytes in patients 
with agammaglobulinemia (inherited lack of immunoglobulins) 
do not have a longer life span at all.