We report a human band 3 alteration that is associated with anemia as determined by a reticulocyte count of 20%. Erythrocyte defects included increased IgG binding, increased breakdown products of band 3, and altered anionand glucose-transport activity in middle-aged cells. These changes were observed during normal erythrocyte aging in situ. Binding of ankyrin to band 3 was normal. Serum/cell crossover studies indicated that a neoantigen appears on the propositus' erythrocytes to which IgG from both propositus and control serum binds as measured with a protein A binding assay. IgG eluted from the propositus' erythrocytes appeared to have a specificity for senescent cell antigen as determined by a phagocytosis inhibition assay. Immunoelectron microscopy showed that antibodies to band 3, which do not normally bind to intact erythrocytes, bound to the propositus' erythrocytes. Antibody 980 binds to normal old cells but not young or middle-aged cells. It also binds to a distinct region of band 3 in immunoblots of membranes from the propositus' middle-aged cells. Cells from both of the propositus' parents exhibited increased IgG binding and altered anion and glucose transport. The results of these studies suggest that (i) band 3 is aging prematurely in erythrocytes from the propositus, (it) senescent cell antigen appears on the propositus' middle-aged red cells, and (Ui) band 3 alterations observed in the propositus may have a genetic component.As part of our ongoing studies on mechanisms of cellular aging, we searched for models of accelerated and decelerated cellular aging. We anticipated that such models would allow us to dissect molecular aging and provide insight into mechanisms. Initially, we investigated models for aging in vitro (1).We subjected intact human erythrocytes to treatments that have been reported to result in changes in band 3 (the major anion-transport polypeptide) and/or to mimic aging in vitro.

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