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Using H-7, HA1001, FK506, cyclosporin A (CsA) and okadaic acid (OA), which are protein kinase and phosphatase inhibitors, we examined qualitative changes in hematopoietic precursor cells due to aging from the viewpoint of the role of protein kinases and phosphatases. Though H-7 and OA suppressed erythroid colony formation both in the elderly (age: 72-92, median: 86) and the young (age: 22-39, median: 29), no change due to aging was noted. HA1001 did not affect erythroid colony formation either in the elderly or the young. Erythroid colony formation was enhanced by FK506 and CsA in the young, however, erythroid colony formation was suppressed in the elderly. Similar examinations using cell fractions of non-T, non-macrophage, non-T + T, and CD34 positive cells were performed in both groups. Enhancement of erythroid colony formation in the young and suppression in the elderly by FK506 using unseparated MNC disappeared after removal of T cells. Enhancement of colony formation in the young and suppression of colony formation in the elderly were recovered when T cells were added again. The effects of FK506 and CsA on erythroid colony formation were thought to be the results of T cell inactivation, and the different sensitivity to FK506 and CsA in the elderly and young seemed to be the result of changes in the control mechanisms of hematopoiesis, such as the regulation of cytokine production by T cells, caused by aging.

The Role of Protein Kinases and Phosphatases in Erythroid Colony Formation of Elderly.