Human bone marrow hematopoietic stem cells are increased in frequency and myeloid-biased with age
Open accessAbstract
In the human hematopoietic system, aging is associated with decreased bone marrow cellularity, decreased adaptive immune system function, and increased incidence of anemia and other hematological disorders and malignancies. Recent studies in mice suggest that changes within the hematopoietic stem cell (HSC) population during aging contribute significantly to the manifestation of these age-associated hematopoietic pathologies. Though the mouse HSC population has been shown to change both quantitatively and functionally with age, changes in the human HSC and progenitor cell populations during aging have been incompletely characterized. To elucidate the properties of an aged human hematopoietic system that may predispose to age-associated hematopoietic dysfunction, we evaluated immunophenotypic HSC and other hematopoietic progenitor populations from healthy, hematologically normal young and elderly human bone marrow samples. We found that aged immunophenotypic human HSC increase in frequency, are less quiescent, and exhibit myeloid-biased differentiation potential compared with young HSC. Gene expression profiling revealed that aged immunophenotypic human HSC transcriptionally up-regulate genes associated with cell cycle, myeloid lineage specification, and myeloid malignancies. These age-associated alterations in the frequency, developmental potential, and gene expression profile of human HSC are similar to those changes observed in mouse HSC, suggesting that hematopoietic aging is an evolutionarily conserved process.
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Although the number of peripheral B cells decreases with age, a more pronounced decrease of B cells in AD was observed, suggesting that ongoing disease may exacerbate ageing effects.
“Although the number of peripheral B cells decreases with age, a more pronounced decrease of B cells in AD was observed, suggesting that ongoing disease may exacerbate ageing effects [88,89].”
From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [89]
The shift toward myeloid potential in aged hematopoietic stem cells correlates with higher expression of myeloid lineage genes and lower expression of lymphoid lineage genes.
“This shift has been correlated with increased expression of myeloid lineage genes and downregulation of those specifying a lymphoid lineage fate (11,17).”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [17]
The most profound immunologic effect of stem cell aging in mice and humans is a reduced ability to generate lymphocytes and an increased myeloid potential.
“From an immunologic perspective, the most profound effect of stem cell aging in both mice (11,18) and humans (17) is a decreased capacity to produce lymphocytes and an increase in myeloid potential.”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [17]
The age-related rise in myeloid lineage gene expression likely comes from accumulation of myeloid-biased hematopoietic stem cells.
“The age-related increase in expression of myeloid lineage genes in the studies noted above (11,17) likely resulted from the accumulation of myeloid-biased HSCs, as these analyses were performed on unseparated pools of HSCs.”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [17]
Hematopoietic stem cells show several age-related changes, including impaired adherence to stromal cells and, in some mouse strains and elderly humans, an increased number.
“HSCs exhibit multiple age-related changes that include impaired adherence to stromal cells and, in some strains of mice (15,16) and elderly humans (17), an increase in number.”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [17]
In humans, an age-dependent rise in putative stem cell frequency coincides with impaired function and reduced lymphoid potential.
“an age-dependent increase in the frequency of putative stem cells, coinciding with impaired functionality and reduced lymphoid potential, has also been in the human system.”
From Aging of hematopoietic stem cells (2018) · cites this paper as [28]
As humans age, they typically experience an increase in total phenotypic HSC numbers as the cell pool grows with time.
“As humans age, they typically experience an increase in total phenotypic HSC numbers as the cell pool grows with time (de Haan and Van Zant, 1999; Pang et al., 2011; Sudo et al., 2000).”
From Unraveling Hematopoiesis through the Lens of Genomics (2020) · cites this paper as Pang et al., 2011
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- Authors
- Pang, W. W., Price, E. A., Sahoo, D., Beerman, I., Maloney, W. J., Rossi, D. J., Schrier, S. L., & Weissman, I. L.
- Affiliations
- Institute for Stem Cell Biology and Regenerative Medicine (IN)
- Department of Internal Medicine, Division of Hematology, and
- Harvard University (US)
- Stanford Medicine (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2011-11-28
- Volume
- 108
- Issue
- 50
- Pages
- 20012-20017
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3250139
- OpenAlex
- W2028815852
- Cited by
- 991
- References
- 49
- Citations by year
- 2026: 79 · 2025: 79 · 2024: 93 · 2023: 87 · 2022: 85 · 2021: 91 · 2020: 83 · 2019: 55 · 2018: 59 · 2017: 54 · 2016: 51 · 2015: 49 · 2014: 63 · 2013: 36 · 2012: 26
- FWCI
- 27.35
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01AG029124)
- National Cancer Institute (R01CA086065, K99CA151673)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Keywords
- hematopoietic stem cells, aging, bone marrow, myeloid differentiation, HSC quiescence, hematopoietic progenitor cells, gene expression profiling, immunophenotype, myeloid neoplasms
- MeSH terms
- Adult, Aged, Aged, 80 and over, Aging, Animals, Bone Marrow Cells, Cell Count, Cell Differentiation, Gene Expression Regulation, Hematopoietic Stem Cells, Humans, Middle Aged, Cell Lineage, Gene Expression Profiling, Myeloid Cells, Mice, Young Adult
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