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 i s unknown, The purpose of the studies was to test the hypothesis that this disregulation might be attributable to altered expression of hema topoietic growth factors. We studied the in vitro ability of cells fro m 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 huma ns, as judged by antibody inhibition studies. In contrast, GM-CSF acco unted for 0-42% of CSA from aged humans. The observation of diminished expression of GM-CSF by cells from aged humans was further accompanie d by a reduced accumulation of mRNA for GM-CSF. In other in vitro stud ies, splenic cells from aged mice released less CSA than cells from yo ung mice, and in vivo experiments showed that splenic cells from mice challenged with E. coli accumulated less mRNA for M-CSF than young mic e. These data demonstrate a similar defect in the expression of hemato poietic growth factors in aged man and mice, We propose that this dimi nished production of bioactive and identifiable hematopoietic growth f actors may be mechanistically important in explaining the disordered h ematopoiesis of aging.