Are the red cell proteases a clock mechanism which turns on a signal of senescence?

The mammalian erythrocyte has a finite life span. In order to study the mechanism involved, a well-defined age group of erythrocytes must be obtained. Such cells are produced by a hypertransfusion system in mice. With this system, it was possible to show that the very oldest population of erythrocytes bind autoantibodies. This binding of the autoantibodies is not a gradual accumulation, but occurs primarily in the oldest red cells. The immunoglobulins bound are not isotype specific but reflect the isotype in the serum. The red cells with the oldest mean age are recognized and phagocytized most readily by peritoneal exudate macrophage in vitro. Earlier studies suggest that protein 3 may be involved in autoantibody binding. An investigation of protein 3 indicates that the human red cells contain well-defined catabolic products of this protein and there is little variation of these catabolic products among individuals both quantitatively and qualitatively. This suggests that there is a well-regulated catabolic system in the red cell. A study of the calcium-activated proteases, the only neutral proteases in the red cell, show that they do not directly generate the amino terminal catabolic fragments of protein 3 found in the erythrocyte.