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Previous Article | Table of Contents | Next Article 
Mouse strain-dependent changes in frequency and proliferation of
hematopoietic stem cells during aging: correlation between lifespan and
cycling activity
G de Haan, W Nijhof and G Van Zant
University of Kentucky Medical Center, Division of Hematology/Oncology,
Markey Cancer Center, Lexington 40536-0093, USA.
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 ranging from
about 500 to 800 days. Stem cell characteristics were determined in young
(6 weeks) and old (12 months) mice. We report striking effects of both
intrinsic strain lifespan and individual mouse age on stem cell
populations. First, the relative and absolute numbers of the most 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 frequencies were calculated,
there was a trend for longer lifespan to be correlated with a larger stem
cell pool. Third, stem cells from old mice had a far lower cycling activity
than cells from young mice. However, this was highly strain dependent:
short-lived C3H/He and CBA/J mice showed a stronger reduction in cycling
activity during aging than long-lived C57BL/6 mice. Finally, a significant
negative correlation was demonstrated in young mice between maximal
lifespan and proliferative activity. 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 related to the maximal lifespan of the mouse strain may open
ways to identify the genetic mechanisms of both strain- and age-dependent
variation in the structure of primitive hematopoietic cell compartments.
Volume 89,
Issue 5,
pp. 1543-1550,
03/01/1997
Copyright © 1997 by The American Society of Hematology

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