MOUSE STRAIN-DEPENDENT CHANGES IN FREQUENCY AND PROLIFERATION OF HEMATOPOIETIC STEM-CELLS DURING AGING - CORRELATION BETWEEN LIFE-SPAN AND CYCLING ACTIVITY

We have quantified the frequency and proliferation of five subsets of primitive hematopoietic cells, using the cobblestone area forming cell (CAFC) assay, in marrow of five strains of mice with lifespans rangin g from about 500 to 800 days. Stem cell characteristics were determine d in young (6 weeks) and old (12 months) mice, We report striking effe cts of both intrinsic strain lifespan and individual mouse age on stem cell populations, First, the relative and absolute numbers of the mos t primitive stem cell subsets was threefold to fourfold higher in old than in young mice, Second, a considerable strain-to-strain variation in the number of primitive cells was observed: when absolute frequenci es were calculated, there was a trend for longer lifespan to be correl ated with a larger stem cell pool. Third, stem cells from old mice had a far lower cycling activity than cells from young mice. However, thi s was highly strain dependent: short-lived C3H/He and CBA/J mice showe d a stronger reduction in cycling activity during aging than long-live d C57BL/6 mice, Finally, a significant negative correlation was demons trated in young mice between maximal lifespan and proliferative activi ty. These data show that aging has a major impact on the frequency and cell-cycle kinetics of primitive hematopoietic cell compartments. In addition, the observation that cycling activity of stem cells is relat ed to the maximal lifespan of the mouse strain may open ways to identi fy the genetic mechanisms of both strain- and age-dependent variation in the structure of primitive hematopoietic cell compartments. (C) 199 7 by The American Society of Hematology.