First Author | Noda S | Year | 2009 |
Journal | Biochem Biophys Res Commun | Volume | 383 |
Issue | 2 | Pages | 210-5 |
PubMed ID | 19345668 | Mgi Jnum | J:148939 |
Mgi Id | MGI:3847164 | Doi | 10.1016/j.bbrc.2009.03.153 |
Citation | Noda S, et al. (2009) Hematopoietic stem cell aging is associated with functional decline and delayed cell cycle progression. Biochem Biophys Res Commun 383(2):210-5 |
abstractText | The molecular mechanisms underlying hematopoietic stem cell (HSC) aging remain to be elucidated. In this study, we investigated age-related changes in the functional and phenotypic properties of murine HSCs. Consistent with previous studies, we found that the number and frequency of CD34(-/low)c-Kit(+)Sca-1(+)lineage marker(-) (CD34(-)KSL) cells, a highly enriched HSC population, significantly increased in old mice, though their repopulating ability was reduced. Continuous bromodeoxyuridine labeling revealed a significant delay in the cell cycle progression of CD34(-)KSL cells in old mice. This delay was also observed in young recipients transplanted with whole bone marrow cells from old mice. When cultured in vitro, CD34(-)KSL cells from old mice showed a greater capacity to give rise to primitive CD48(-)KSL cells with reduced HSC activity. Gene expression profiling identified age-related changes in the expression of several cell cycle regulatory genes, including p21/Cdkn1a and p18/Cdkn2c. These results support the notion that HSC aging is largely regulated by an intrinsic genetic program. |