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(The FASEB Journal. 1999;13:707-713.)
© 1999 FASEB


Research Communications

Genetic analysis of hemopoietic cell cycling in mice suggests its involvement in organismal life span

GERALD DE HAANa,b and GARY VAN ZANTa


a Blood and Marrow Transplant Program, Division of Hematology/Oncology, University of Kentucky Medical Center, Lexington, Kentucky 40536-0093, USA; and

b Department of Physiological Chemistry, University of Groningen, Groningen, The Netherlands

Normal somatic cells undergo replicative senescence in vitro but the significance of this process in organismic aging remains controversial. We have shown previously that hemopoietic stem cells of common inbred strains of mice vary widely in cycling activity and that this parameter is inversely correlated with strain-dependent mean life span. To assess whether cell cycling and life span are causally related, we searched for quantitative trait loci (QTLs) that contributed to variation of these traits in BXH and BXD recombinant inbred mice. Two QTLs, mapping to exactly the same intervals on chromosomes 7 and 11, were identified that were associated with variation of both cell cycling and life span. The locus on chromosome 11 mapped to the cytokine cluster, a segment that shows synteny with human chromosome 5q, in which deletions are strongly associated with myelodysplastic syndrome. These data indicate that steady-state cell turn-over, here measured in hemopoietic progenitor cells, may have a significant effect on the mean life span of mammals. de Haan, G., Van Zant, G. Genetic analysis of hemopoietic cell cycling in mice suggests its involvement in organismal life span.


Key Words: stem cells • longevity • cell proliferation • aging • quantitative trait locus




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