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

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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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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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