The DOI matches its Crossref record; 158 of the 158 references it cites were found in a registry or an index.
Changes in primary lymphoid organs with aging
Open accessAbstract
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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“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]
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“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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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
Understanding immunosenescence to improve responses to vaccines
Goronzy, J. J., & Weyand, C. M. (2013) · Nature Immunology · doi:10.1038/ni.2588 · Cited by 827
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Metadata
- 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.
- Venue
- Seminars in Immunology
- Publisher
- Elsevier BV
- Published
- 2012-10
- Volume
- 24
- Issue
- 5
- Pages
- 309-320
- ISSN
- 1044-5323 (ISSN-L)
- 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
- 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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