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.
Chatta
G S
GS
Department of Medicine, University of Washington School of Medicine, Seattle.
Andrews
R G
RG
Rodger
E
E
Schrag
M
M
Hammond
W P
WP
Dale
D C
DC
D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D015703:Antigens, CD / Q000032:analysis; D001854:Bone Marrow Cells; D002455:Cell Division; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000502:physiology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D006801:Humans; D007377:Interleukin-3 / Q000008:administration & dosage / Q000502:physiology*; D008297:Male
D015703:Antigens, CD; D007377:Interleukin-3; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor