MOUSE STRAIN-DEPENDENT CHANGES IN FREQUENCY AND PROLIFERATION OF HEMATOPOIETIC STEM-CELLS DURING AGING - CORRELATION BETWEEN LIFE-SPAN AND CYCLING ACTIVITY
G. Dehaan et al., MOUSE STRAIN-DEPENDENT CHANGES IN FREQUENCY AND PROLIFERATION OF HEMATOPOIETIC STEM-CELLS DURING AGING - CORRELATION BETWEEN LIFE-SPAN AND CYCLING ACTIVITY, Blood, 89(5), 1997, pp. 1543-1550
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.