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 h ematopoietic progenitors may be a major factor accounting for age-rela ted changes in stimulus driven hematopoiesis. Methods. To test these h ypotheses, 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 vi tro marrow culture system. Results. There was no age-related differenc e 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-respons e studies with individual growth factors revealed a 2-fold decrease in sensitivity of the elderly subjects' cells to G-CSF (p < .01). Conclu sions. Aging has little impact on the marrow content of early precurso rs of the neutrophil lineage. There is, however, a significant differe nce in the in vitro proliferative response of these cells to the linea ge specific growth factor G-CSF. This alteration may account for the g reater propensity in elderly populations for the development of neutro penia with severe infections and chemotherapy.