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

Normal somatic cells undergo replicative senescence in vitro but the signif icance of this process in organismic aging remains controversial. We have s hown previously that hemopoietic stem cells of common inbred strains of mic e vary widely in cycling activity and that this parameter is inversely corr elated with strain-dependent mean life span, To assess whether cell cycling and life span are causally related, we searched for quantitative trait loc i (QTLs) that contributed to variation of these traits in BXH and BXD recom binant inbred mice. Two QTLs, mapping to exactly the same intervals on chro mosomes 7 and 11, were identified that were associated with variation of bo th cell cycling and life span. The locus on chromosome II mapped to the cyt okine cluster, a segment that shows synteny with human chromosome 5q, in wh ich deletions are strongly associated with myelodysplastic syndrome. These data indicate that steady-state cell turn-over, here measured in hemopoieti c progenitor cells, may have a significant effect on the mean life span of mammals.