Decline in the growth potential of spleen-colonizing bone marrow stem cells of long-lived aging mice.

Abstract

The growth capacity of femoral bone marrow stem cells from young and old long-lived mice was assessed in the spleen of X-irradiated young and old syngeneic recipients by determining the number of stem cells colonizing the spleen, the rate of incorporation of 125I-labeled iododeoxyuridine by proliferating colony cells, and the number of cells present in the largest colonies at the end of the growth phase. The growth capacity of stem cells declined with age. The spleen-seeking and spleen colony growth capacities of old stem cells remained characteristically old even after they were allowed to self-replicate in the bone marrow of young recipients for an extended period of time. The spleen colony growth capacity of young stem cells could be reduced by allowing them to self-replicate in old recipients. The growth capacity of old stem cells is apparently an intrinsic characteristic which cannot be readily altered, but that of young stem cells can apparently be aged in an accelerated manner by allowing them to self-replicate in old recipients. An additional reduction was noted in the frequency of young and old stem cells colonizing the spleen of old recipients and in the cell density of the largest colonies produced. Factors extrinsic to the stem cells are probably also responsible for the decline with age in their spleen colony growth capacity. The growth capacity of old stem cells in old recipients could be as low as 10% that of young stem cells in young recipients.