Changes in primary lymphoid organs with aging

Chinn, Ivan K.; Blackburn, Clare C.; Manley, Nancy R.; Sempowski, Gregory D.

doi:10.1016/j.smim.2012.04.005

Cited by 282T-cell and B-cell ImmunologyHematopoietic Stem Cell TransplantationGenetics, Aging, and Longevity in Model Organisms

Changes in primary lymphoid organs with aging

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Chinn, Ivan K., Blackburn, Clare C., Manley, Nancy R., Sempowski, Gregory D.·2012·Seminars in Immunology

DOI 10.1016/j.smim.2012.04.005PMC PMC3415579

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Abstract

Aging is associated with decreased immune function that leads to increased morbidity and mortality in the elderly. Immune senescence is accompanied by age-related changes in two primary lymphoid organs, bone marrow and thymus, that result in decreased production and function of B and T lymphocytes. In bone marrow, hematopoietic stem cells exhibit reduced self-renewal potential, increased skewing toward myelopoiesis, and decreased production of lymphocytes with aging. These functional sequelae of aging are caused in part by increased oxidative stress, inflammation, adipocyte differentiation, and disruption of hypoxic osteoblastic niches. In thymus, aging is associated with tissue involution, exhibited by a disorganization of the thymic epithelial cell architecture and increased adiposity. This dysregulation correlates with a loss of stroma-thymocyte 'cross-talk', resulting in decreased export of naïve T cells. Mounting evidence argues that with aging, thymic inflammation, systemic stress, local Foxn1 and keratinocyte growth factor expression, and sex steroid levels play critical roles in actively driving thymic involution and overall adaptive immune senescence across the lifespan. With a better understanding of the complex mechanisms and pathways that mediate bone marrow and thymus involution with aging, potential increases for the development of safe and effective interventions to prevent or restore loss of immune function with aging.

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Degeneration of the thymus is the cause of age-related failure of the adaptive immune system.
“Therefore, degeneration of the thymus is the cause of age-related failure of the adaptive immune system [95, 96].”
From Immunosenescence: a key player in cancer development (2020) · cites this paper as [96]
Production of inflammatory mediators that may be toxic to thymocytes increases with age.
“In addition, the production of inflammatory mediators that may be thymocytotoxic also increases with age (39).”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [39]

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Lymphohematopoietic progenitors do not have a synchronized defect with age‐related thymic involution
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On the relationship of the thymus to the sexual organs1
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Concentration of adipogenic and proinflammatory cytokines in the bone marrow supernatant fluid of osteoporotic women
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The Murine Thymic Microenvironment: Changes with Age
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Normal immunoglobulin G protects against experimental allergic encephalomyelitis by inducing transferable T cell unresponsiveness to myelin basic protein
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Bone Marrow Gas Tensions, Bone Marrow Blood Flow, and Erythropoiesis in Man
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FGFR2IIIb signaling regulates thymic epithelial differentiation
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Reduced number of VSELs in the bone marrow of growth hormone transgenic mice indicates that chronically elevated Igf1 level accelerates age-dependent exhaustion of pluripotent stem cell pool: a novel view on aging
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Reactive oxygen species produced in mitochondria are involved in age-dependent changes of hematopoietic and mesenchymal progenitor cells in mice. A study with the novel mitochondria-targeted antioxidant SkQ1
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Coordinating Development of Medullary Thymic Epithelial Cells
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The twilight of immunity: emerging concepts in aging of the immune system
Nikolich-Žugich, J. (2018) · Nature Immunology · doi:10.1038/s41590-017-0006-x · Cited by 1,240 · see citing works
Understanding immunosenescence to improve responses to vaccines
Goronzy, J. J., & Weyand, C. M. (2013) · Nature Immunology · doi:10.1038/ni.2588 · Cited by 827 · see citing works
Causes, consequences, and reversal of immune system aging
Montecino-Rodriguez, E., Berent-Maoz, B., & Dorshkind, K. (2013) · Journal of Clinical Investigation · doi:10.1172/jci64096 · Cited by 793 · see citing works
SARS-CoV-2 and COVID-19 in older adults: what we may expect regarding pathogenesis, immune responses, and outcomes
Nikolich-Zugich, J., Knox, K. S., Rios, C. T., Natt, B., Bhattacharya, D., & Fain, M. J. (2020) · GeroScience · doi:10.1007/s11357-020-00186-0 · Cited by 577 · see citing works
Immunosenescence: a key player in cancer development
Lian, J., Yue, Y., Yu, W., & Zhang, Y. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00986-z · Cited by 510 · see citing works
Senescent cell clearance by the immune system: Emerging therapeutic opportunities
Prata, L. G. P. L., Ovsyannikova, I. G., Tchkonia, T., & Kirkland, J. L. (2018) · Seminars in Immunology · doi:10.1016/j.smim.2019.04.003 · Cited by 497 · see citing works
The Effect of Age on Thymic Function
Palmer, D. B. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00316 · Cited by 494 · see citing works
Contributions of Age-Related Thymic Involution to Immunosenescence and Inflammaging
Thomas, R., Wang, W., & Su, D.-M. (2020) · Immunity & Ageing · doi:10.1186/s12979-020-0173-8 · Cited by 442 · see citing works
Successful and Maladaptive T Cell Aging
Goronzy, J. J., & Weyand, C. M. (2017) · Immunity · doi:10.1016/j.immuni.2017.03.010 · Cited by 362 · see citing works
Naive T Cell Maintenance and Function in Human Aging
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Self-citation

Authors: Chinn, I. K., Blackburn, C. C., Manley, N. R., & Sempowski, G. D.
Affiliations: Duke Medical Center (US)
MRC Centre for Regenerative Medicine (GB)
University of Georgia (US)
Corresponding author: Sempowski, Gregory D.
ORCID: Chinn, Ivan K.
Blackburn, Clare C.
Manley, Nancy R.
Sempowski, Gregory D.
Venue: Seminars in Immunology
Publisher: Elsevier BV
Published: 2012-10
Volume: 24
Issue: 5
Pages: 309-320
ISSN: 1044-5323 (ISSN-L)
DOI: 10.1016/j.smim.2012.04.005
PMC: PMC3415579
OpenAlex: W2136991900
Cited by: 282
References: 158
Citations by year: 2026: 12 · 2025: 8 · 2024: 17 · 2023: 14 · 2022: 26 · 2021: 23 · 2020: 31 · 2019: 26 · 2018: 25 · 2017: 18 · 2016: 20 · 2015: 22 · 2014: 20 · 2013: 17 · 2012: 3
FWCI: 1.79
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Seminars in Immunology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: Leukaemia and Lymphoma Research
Directorate for Biological Sciences
Biotechnology and Biological Sciences Research Council (BB/H021183/1)
National Institute on Aging (AG035302, AG-025150, R01AG035302, R01AG025150)
National Institute of Allergy and Infectious Diseases (R01AI082127, HHSN272200900059C, R01AI055001, AI076514, AI082127, UC6AI058607, P01AI076514)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD043494, K12HD043494)
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Keywords: immunosenescence, aging, primary lymphoid organs, thymic involution, hematopoietic stem cells, myelopoiesis, oxidative stress, Foxn1, keratinocyte growth factor, sex steroids, adipose tissue, B cells, T cells
MeSH terms: Aging, Animals, Bone Marrow, Humans, Immunity, Innate, Lymphatic System, Cell Hypoxia, Oxidative Stress

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Changes in primary lymphoid organs with aging

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