Normal production of erythrocytes by mouse marrow continuous for 73 months

Abstract

Marrow cell transplants from old and young control donors were carried in genetically anemic W/W(v) recipients whose anemias were cured by successful transplants. After maximum of 36 months and four serial transplants, marrow cell lines from both old and younger control donors continued to produce erythrocytes normally. The oldest marrow cell lines had produced erythrocytes normally for 73 months. NORMAL ERYTHROCYTE PRODUCTION WAS DEMONSTRATED BY: (1) cure of the anemia in W/W(v) recipients, (2) normal rather than delayed recovery rate of cured recipients after severe bleeding, and (3) normal rather than ineffective response of cured recipients to erythropoietin. Hemoglobin patterns, tested in cured W/W(v) recipients after the first transplantation, showed that at least 90% of the circulating erythrocytes were of the donor type even in donor lines that had produced erythrocytes continuously for 45 months and were recovering from severe bleeding. Concentrations of cells capable of forming macroscopic spleen colonies were more than two orders of magnitude higher in W/W(v) mice cured by old or younger marrow than in uncured W/W(v) mice. Nevertheless, colony-forming unit concentrations declined slowly with successive transplants, and the decline seemed more pronounced at the fourth transplant in old than in younger cell lines.The hypothesis is suggested that senescence is caused by declines in function of only a few vital cell types. The system for comparing old and younger marrow cell lines offers a model for experiments to test this hypothesis and to identify the cell types whose decline causes aging.