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Hematopoietic stem cell aging and self-renewal

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Abstract

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.

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Acknowledgements

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

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  1. Department of Cell Biology, Section Stem Cell Biology, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, Groningen, 9713 AV, The Netherlands

    Brad Dykstra & Gerald de Haan

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  1. Brad Dykstra
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  2. Gerald de Haan
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Correspondence to Brad Dykstra.

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We are grateful for the generous financial support provided by the Dutch Platform for Tissue Engineering (to B.D.) and for a VICI grant awarded by the Netherlands Organization for Scientific Research (to G.d.H.).

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Dykstra, B., de Haan, G. Hematopoietic stem cell aging and self-renewal. Cell Tissue Res 331, 91–101 (2008). https://doi.org/10.1007/s00441-007-0529-9

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