Impaired expression of hematopoietic growth factors: a candidate mechanism for the hematopoietic defect of aging.

Aged humans and aged experimental animals exhibit a diminished ability to upregulate hematopoiesis, but the mechanism responsible for this is unknown. The purpose of the studies was to test the hypothesis that this disregulation might be attributable to altered expression of hematopoietic growth factors. We studied the in vitro ability of cells from aged humans or mice to release bioactive colony stimulating activity (CSA) and to accumulate mRNA for defined growth factors. Human light density leukocytes from the aged released less CSA than cells from the young. GM-CSF accounted for 72-100% of the CSA released by young humans, as judged by antibody inhibition studies. In contrast, GM-CSF accounted for 0-42% of CSA from aged humans. The observation of diminished expression of GM-CSF by cells from aged humans was further accompanied by a reduced accumulation of mRNA for GM-CSF. In other in vitro studies, splenic cells from aged mice released less CSA than cells from young mice, and in vivo experiments showed that splenic cells from mice challenged with E. coli accumulated less mRNA for M-CSF than young mice. These data demonstrate a similar defect in the expression of hematopoietic growth factors in aged man and mice. We propose that this diminished production of bioactive and identifiable hematopoietic growth factors may be mechanistically important in explaining the disordered hematopoiesis of aging.