The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.
The impact of altered p53 dosage on hematopoietic stem cell dynamics during aging
Open accessAbstract
A temporal decline in tissue stem cell functionality may be a key component of mammalian aging. The tumor suppressor p53 has recently been implicated as a potential regulator of aging. We examined age-associated hematopoietic stem cell (HSC) dynamics in mice with varying p53 activities. Reduced p53 activity in p53+/− mice was associated with higher numbers of proliferating hematopoietic stem and progenitor cells in old age compared with aged wild-type (p53+/+) mice. We also assessed HSC dynamics in a p53 mutant mouse model (p53+/m) with higher apparent p53 activity than wild-type mice. The p53 hypermorphic (p53+/m) mice display phenotypes of premature aging. Many aged p53+/m organs exhibit reduced cellularity and atrophy, suggesting defects in stem-cell regenerative capacity. HSC numbers from old p53+/m mice fail to increase with age, unlike those of their p53+/+ and p53+/− counterparts. Moreover, transplantation of 500 HSCs from old p53+/m mice into lethally irradiated recipients resulted in reduced engraftment compared with old wild-type p53+/+ and p53+/− HSCs. Thus, alteration of p53 activity affects stem-cell numbers, proliferation potential, and hematopoiesis in older organisms, supporting a model in which aging is caused in part by a decline in tissue stem cell regenerative function.
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Cites
Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours
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Self-citationp53 mutant mice that display early ageing-associated phenotypes
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“Mice: All p53 mutant mice used in this study were generated and reported previously by our laboratory.(12,23) The wild type and p53 deficient mice were produced by p53 heterozygote crossings and genotyped by Southern blot analysis, using a murine p53 exon 5-10 cDNA probe to genomic tail DNA cleaved with Bam HI as desc…”
BackgroundMethodInfluentialSelf-citationStem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a
Janzen, V., Forkert, R., Fleming, H. E., Saito, Y., Waring, M. T., Dombkowski, D. M., Cheng, T., DePinho, R. A., Sharpless, N. E., & Scadden, D. T. (2006) · Nature · doi:10.1038/nature05159 · Cited by 1,106
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Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis during ageing
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Self-citationAccelerated ageing in mice deficient in Zmpste24 protease is linked to p53 signalling activation
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Cited by
Stems Cells and the Pathways to Aging and Cancer
Rossi, D. J., Jamieson, C. H. M., & Weissman, I. L. (2008) · Cell · doi:10.1016/j.cell.2008.01.036 · Cited by 895
Aging Hematopoietic Stem Cells Decline in Function and Exhibit Epigenetic Dysregulation
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Self-citationp53 Regulates Hematopoietic Stem Cell Quiescence
Liu, Y., Elf, S. E., Miyata, Y., Sashida, G., Liu, Y., Huang, G., Di Giandomenico, S., Lee, J. M., Deblasio, A., Menendez, S., et al. (2009) · Cell Stem Cell · doi:10.1016/j.stem.2008.11.006 · Cited by 547
DNA repair is limiting for haematopoietic stem cells during ageing
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Aging and Replicative Senescence Have Related Effects on Human Stem and Progenitor Cells
Wagner, W., Bork, S., Horn, P., Krunic, D., Walenda, T., Diehlmann, A., Benes, V., Blake, J., Huber, F.-X., Eckstein, V., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005846 · Cited by 477
Metadata
- Authors
- Dumble, M., Moore, L., Chambers, S. M., Geiger, H., Van Zant, G., Goodell, M. A., & Donehower, L. A.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2006-10-10
- Volume
- 109
- Issue
- 4
- Pages
- 1736-1742
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2148479228
- Cited by
- 241
- References
- 15
- FWCI
- 12.07
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Dumble, M., Moore, L., Chambers, S. M., Geiger, H., Van Zant, G., Goodell, M. A., & Donehower, L. A. (2007). The impact of altered p53 dosage on hematopoietic stem cell dynamics during aging. Blood. https://doi.org/10.1182/blood-2006-03-010413
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