Investigations into mechanisms by which macrophages distinguish mature from senescent self revealed that a Mr ∼ 62,000 glycoprotein, the senescent cell antigen, appears on the surface of senescent and damaged cells. It is recognized by the antigen-binding Fab region of a specific IgG autoantibody in serum which attaches to cells carrying the senescent cell antigen and initiates their removal by macrophages. The senescent cell antigen was first observed on the surface of senescent human erythrocytes but has since been demonstrated on all cells examined. Senescent cell antigen appears to be derived from band 3, the major anion transport protein of the erythrocyte. The current working hypothesis is that degradation of band 3 causes a conformational change in its tertiary structure that generates the senescent cell antige