Immunoaging induced by hematopoietic stem cell aging
Abstract
Hematopoietic stem cells (HSCs) generate all known hematopoietic lineages and self-renew, but the function of HSCs declines during aging, which is characterized as impairments of lymphopoiesis and enhanced myelopoiesis. These aging-associated changes correlate with an increasing risk of myelo-proliferative diseases and impairments in immune function. Recent studies showed that only a subpopulation of HSCs contains a high capacity to undergo lymphoid differentiation but this subpopulation is lost during aging, which contributes to age-related impairments in lymphopoiesis. On the basis of the observations that DNA damage and telomere dysfunction can impair stem cell function, it is possible that accumulation of DNA damage results in the loss of subpopulations of HSCs that are required for the maintenance of lymphopoiesis and immune functions during aging.
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The proportion of CD56bright NK cells appears reduced in the elderly, likely due to impaired production of new NK cells from the bone marrow.
“The proportion of CD56bright NK cells appears to be reduced in the elderly, which is likely the consequence of an impaired production of new NK cells with advanced age, due to a lower output from the bone marrow [98].”
From Aging of the immune system: Focus on inflammation and vaccination (2016) · cites this paper as [98]
The innate immune response declines with age.
“The innate immune response also declines with age.”
From Evolution of the immune system in humans from infancy to old age (2015) · cites this paper as [94]
Changes in innate cell numbers occur with age, with skewing of haematopoiesis towards the myeloid lineages.
“There are changes in innate cell numbers, with skewing of haematopoiesis towards the myeloid lineages [93,94].”
From Evolution of the immune system in humans from infancy to old age (2015) · cites this paper as [94]
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“Functional impairments of the immune system with aging are at least partly related to the age-related dysregulation of hematopoiesis [5].”
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“Nevertheless, the immune system decline associated with aging can be partially responsible for senescent cells’ accumulation in organisms with increased age [82].”
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Self-citationImmunosenescence and lymphomagenesis
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Müller, L., & Benedetto, S. D. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1298004 · Cited by 49 · see citing works
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“The production of erythrocytes is often reduced in elderly people, leading to anemia,(9) and acquired immunity becomes less effective with aging, which can result in increased susceptibility to infectious diseases and malignancy in the elderly.(10,11) In contrast, the production of myeloid cells often increases with a…”
BackgroundInflammaging, immunosenescence, and cardiovascular aging: insights into long COVID implications
Müller, L., & Benedetto, S. D. (2024) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2024.1384996 · Cited by 43 · see citing works
Immunosenescence and inflammaging: Mechanisms and modulation through diet and lifestyle
Müller, L., & Benedetto, S. D. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1708280 · Cited by 46 · see citing works
“With advancing age, HSCs undergo functional decline characterized by reduced self-renewal capacity, accumulation of DNA damage, epigenetic alterations, and metabolic dysfunction (22).”
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Are aging biomarkers clinically relevant in oncogeriatrics?
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“[4] Wang J, Geiger H, Rudolph KL.”
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“Although the low levels of telomerase activity displayed by hematopoietic stem cells are sufficient to ensure long-term survival, they do not appear to prevent age-associated telomere erosion in these cells [50].”
BackgroundAge-And Gender-Related Pattern of Methylation in the MT-RNR1 Gene
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Cdc42-Borg4-Septin7 axis regulates HSC polarity and function
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“The aging-related changes in HSCs and hematopoiesis are caused by both cell intrinsic alterations in HSCs and extrinsic BM niche factors (Kamminga & de Haan, 2006; Geiger et al , 2007; Wang et al , 2011; Guidi et al , 2017; Sac¸ma et al , 2019; Mejia-Ramirez & Florian, 2020).”
Self-citationAging‐ and vascular‐related pathologies
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Cadmium Activates Noncanonical Wnt Signaling to Impair Hematopoietic Stem Cell Function in Mice
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An old problem with new solutions: Strategies to improve vaccine efficacy in the elderly
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Müller, L., & Benedetto, S. D. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1393324 · Cited by 25 · see citing works
“Moreover, accumulated genetic and epigenetic changes in HSCs with age further contribute to their dysfunction, increasing the susceptibility to hematologic malignancies and immune-related disorders (36, 39 – 41).”
BackgroundShorter Ends, Faster End? Leukocyte Telomere Length and Mortality Among Older Taiwanese
Glei, D. A., Goldman, N., Weinstein, M., & Risques, R. A. (2014) · The Journals of Gerontology Series A · doi:10.1093/gerona/glu191 · Cited by 25 · see citing works
“Moreover, their percentage increases with age, as observed here, most likely due to a decrease of lymphopoiesis in the elderly (41).”
BackgroundStem cells and aging: a chicken-or-the-egg issue?
Smith, J. A., & Daniel, R. (2012) · Europe PMC (PubMed Central) · Cited by 23 · see citing works
Neuroimmune dynamics and brain aging: mechanisms and consequences
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“Telomere shortening, epigenetic drift, and accumulation of DNA damage in progenitor cells contribute to these shifts (Wang et al., 2011; Wells et al., 2024).”
Age-related reduction of structural complexity in spleen hematopoietic tissue architecture in mice
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“Aging-associated changes also affect committed developing B cells, in particular maturation of pro-B cells to pre-B cells (12).”
BackgroundImmunological aspects of age-related diseases
Isobe, K., Nishio, N., & Hasegawa, T. (2017) · World Journal of Biological Chemistry · doi:10.4331/wjbc.v8.i2.129 · Cited by 21 · see citing works
Hematopoietic Stem Cell Heterogeneity
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CD137 ligand reverse signaling skews hematopoiesis towards myelopoiesis during aging
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Biomarkers of Senescence during Aging as Possible Warnings to Use Preventive Measures
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“Genetic [17] and microenvironmental [18] factors related to aging may be responsible for the changes in hematopoietic stem cell populations that select for myeloid precursor cells and result in a relative decrease of lymphoid progenitors, and centenarian studies have shown that the linear decline of lymphocyte numbers…”
BackgroundAge-associated systemic factors change central and peripheral immunity in adult male mice
van Olst, L., Kamermans, A., van der Pol, S. M. A., Rodríguez, E., Hulshof, L. A., van Dijk, R. E., Vonk, D., Schouten, M., Witte, M. E., de Vries, H. E., et al. (2023) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2023.05.004 · Cited by 10 · see citing works
A Simple Model System Enabling Human CD34+ Cells to Undertake Differentiation Towards T Cells
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Aging immunity: unraveling the complex nexus of diet, gut microbiome, and immune function
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“One major alteration is a shift in hematopoiesis, which favors myeloid lineage cells such as cDCs, over lymphoid lineage cells such as pDCs [39,40] .”
Immunomodulatory strategies for immune dysregulation following severe musculoskeletal trauma
Vantucci, C. E., Roy, K., & Guldberg, R. E. (2018) · Journal of Immunology and Regenerative Medicine · doi:10.1016/j.regen.2018.07.001 · Cited by 9 · see citing works
Cellular signalling pathways in immune aging and regeneration
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Phenotypes, mechanisms, and therapeutic strategies of natural killer cell immunosenescence
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“Decreased levels of CD56 bright NK cells in the elderly could be due to age-associated changes in both the quantity and functionality of hematopoietic stem cells, alongside a diminished capacity for generating new NK cells [20, 31].”
The wild mouse bone marrow has a unique myeloid and lymphoid composition and phenotype
Muir, A., Bennett, A., Smith, H., Logunova, L., Wolfenden, A., Fenn, J., Lowe, A., Brass, A., Grainger, J. R., Konkel, J. E., et al. (2023) · Discovery Immunology · doi:10.1093/discim/kyad005 · Cited by 7 · see citing works
“The absence of any changes in the myeloid/lymphoid ratio in the current study may be explained by the fact that the retired breeders were only 6 months old, with the age asscociated increases in myelopoieisis typically only arising in mice at a much older 1–2 years of age [16, 17].”
BackgroundResultInfluentialMolecular Determinants of Atherosclerosis
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Regulation of Myelopoiesis by CD137L Signaling
Tang, Q., Jiang, D., Harfuddin, Z., Cheng, K., Moh, M. C., & Schwarz, H. (2014) · International Reviews of Immunology · doi:10.3109/08830185.2014.921163 · Cited by 6 · see citing works
“Hematopoiesis has been known to be skewed towards myelopoiesis during aging resulting in a much compromised lymphopoiesis [51].”
BackgroundLoss of GADD34 induces early age‐dependent deviation to the myeloid lineage
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Common marmoset CD117 + hematopoietic cells possess multipotency
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Sirtuins and the prevention of immunosenescence
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BackgroundTelomere Biology in Senescence and Aging
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Myeloid-Derived Suppressor Cells in Aged Humans
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“The function of hematopoietic stem cells declines with aging, resulting in decreased lymphopoiesis and increased myelopoiesis, an consequently impaired immune function (Wang et al. 2011).”
BackgroundSearching for Clinically Relevant Biomarkers in Geriatric Oncology
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“To name a few, the ageing of the hematopoietic system, which is one of the most studied and best characterized systems due to tissue accessibility by peripheral blood sampling, is marked by decrease in lymphopoiesis (often referred to by “immunosenescence” [11]) and a relative increase of myelopoiesis, possibly becaus…”
BackgroundMultitasking Roles for Poly(ADP-ribosyl)ation in Aging and Longevity
Mangerich, A., & Bürkle, A. (2015) · Cancer drug discovery and develogment/Cancer drug discovery and development · doi:10.1007/978-3-319-14151-0_6 · Cited by 2 · see citing works
“, an age-related decline in the capacity of adaptive immunity, consisting of more specific responses carried out by B and T-cells [313].”
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Self-citation
- Authors
- Wang, J., Geiger, H., & Rudolph, K. L.
- Affiliations
- Universität Ulm (DE)
- Cincinnati Children's Hospital Medical Center (US)
- Corresponding author
- Rudolph, K Lenhard
- Venue
- Current Opinion in Immunology
- Publisher
- Elsevier BV
- Published
- 2011-08
- Volume
- 23
- Issue
- 4
- Pages
- 532-536
- ISSN
- 0952-7915 (ISSN-L)
- OpenAlex
- W2170352596
- Semantic Scholar
- 8b3a2c42088c6d10f70fd28be811af503753cada
- Cited by
- 107
- References
- 51
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 5 · 2023: 4 · 2022: 6 · 2021: 5 · 2020: 4 · 2019: 8 · 2018: 12 · 2017: 9 · 2016: 6 · 2015: 7 · 2014: 11 · 2013: 12 · 2012: 10
- FWCI
- 1.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Opinion in Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Deutsche Krebshilfe
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- hematopoietic stem cell aging, immunosenescence, lymphocyte development, myelopoiesis, myeloproliferative neoplasms, DNA damage, telomere dysfunction, lymphoid differentiation, immune function decline
- MeSH terms
- Signaling Lymphocytic Activation Molecule Family Member 1, Aging, Animals, Cell Division, Clone Cells, DNA Damage, Hematopoietic Stem Cells, Humans, Myeloproliferative Disorders, Receptors, Cell Surface, Thymus Gland, Antigens, CD, Lymphocyte Subsets, Telomere, Reactive Oxygen Species, Cell Lineage, Lymphopoiesis, Myelopoiesis, Mice, Immunity, Humoral
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