Cell and Tissue Research

, Volume 331, Issue 1, pp 91–101 | Cite as

Hematopoietic stem cell aging and self-renewal

  • Brad DykstraEmail author
  • Gerald de Haan


A functional decline of the immune system occurs during organismal aging that is attributable, in large part, to changes in the hematopoietic stem cell (HSC) compartment. In the mouse, several hallmark age-dependent changes in the HSC compartment have been identified, including an increase in HSC numbers, a decrease in homing efficiency, and a myeloid skewing of differentiation potential. Whether these changes are caused by gradual intrinsic changes within individual HSCs or by changes in the cellular composition of the HSC compartment remains unclear. However, of note, many of the aging properties of HSCs are highly dependent on their genetic background. In particular, the widely used C57Bl/6 strain appears to have unique HSC aging characteristics compared with those of other mouse strains. These differences can be exploited by using recombinant inbred strains to further our understanding of the genetic basis for HSC aging. The mechanism(s) responsible for HSC aging have only begun to be elucidated. Recent studies have reported co-ordinated variation in gene expression of HSCs with age, possibly as a result of epigenetic changes. In addition, an accumulation of DNA damage, in concert with an increase in intracellular reactive oxygen species, has been associated with aged HSCs. Nevertheless, whether age-related changes in HSCs are programmed to occur in a certain predictable fashion, or whether they are simply an accumulation of random changes over time remains unclear. Further, whether the genetic dysregulation observed in old HSCs is a cause or an effect of cellular aging is unknown.


Hematopoietic stem cell Aging (organismal/cellular) Self-renewal Genetical genomics ROS C57Bl/6 DBA/2 



We thank D. Kent and R. van Os for critical reading of the manuscript.


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© Springer-Verlag 2007

Authors and Affiliations

  1. 1.Department of Cell Biology, Section Stem Cell Biology, University Medical Center GroningenUniversity of GroningenGroningenThe Netherlands

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