HEMATOPOIETIC PROGENITORS AND AGING - ALTERATIONS IN GRANULOCYTIC PRECURSORS AND RESPONSIVENESS TO RECOMBINANT HUMAN G-CSF, GM-CSF, AND IL-3

Background. Changes either in the number or in the responsiveness of hematopoietic progenitors may be a major factor accounting for age-related changes in stimulus driven hematopoiesis. Methods. To test these hypotheses, we compared the relative proportions and the responsiveness of CD34+ bone marrow cells from healthy young (20-30 yrs) and healthy elderly (70-80 yrs) volunteers to G-CSF, GM-CSF, and IL-3 in an in vitro marrow culture system. Results. There was no age-related difference either in the proportion of CD34+ marrow cells or in the proportion of a more mature CD34+ subset, defined as CD34+, CD33+ cells. Maximal colony formation by CD34+ cells stimulated with a combination of G-CSF, GM-CSF, and IL-3 was similar in the two groups, but the dose-response studies with individual growth factors revealed a 2-fold decrease in sensitivity of the elderly subjects' cells to G-CSF (p < .01). Conclusions. Aging has little impact on the marrow content of early precursors of the neutrophil lineage. There is, however, a significant difference in the in vitro proliferative response of these cells to the lineage specific growth factor G-CSF. This alteration may account for the greater propensity in elderly populations for the development of neutropenia with severe infections and chemotherapy.