Lymphocyte maintenance during healthy aging requires no substantial alterations in cellular turnover
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In healthy humans, lymphocyte populations are maintained at a relatively constant size throughout life, reflecting a balance between lymphocyte production and loss. Given the profound immunological changes that occur during healthy aging, including a significant decline in T-cell production by the thymus, lymphocyte maintenance in the elderly is generally thought to require homeostatic alterations in lymphocyte dynamics. Surprisingly, using in vivo (2) H2 O labeling, we find similar dynamics of most lymphocyte subsets between young adult and elderly healthy individuals. As the contribution of thymic output to T-cell production is only minor from young adulthood onward, compensatory increases in peripheral T-cell division rates are not required to maintain the T-cell pool, despite a tenfold decline in thymic output. These fundamental insights will aid the interpretation of further research into aging and clinical conditions related to disturbed lymphocyte dynamics.
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Daily turnover of naive CD4+ and CD8+ T cells remains stable at about 0.04% throughout adulthood, with no apparent compensatory increase in homeostatic proliferation with age.
“Daily turnover rates of naive CD4+ and CD8+ T cells are stable throughout adulthood at about 0.04%, with no apparent need for compensatory increase in homeostatic proliferation with age.”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Westera et al., 2015
In later life, naive CD8+ T cells accelerate turnover.
“Only in later life, naive CD8+ T cells accelerate their turnover”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Westera et al., 2015
In young adults the thymus contributes only 16% of total T cell generation, and in older individuals thymic contribution falls below 1%, so they rely almost entirely on peripheral proliferation.
“Even in young adults, the thymus contributes only 16% of total T cell generation. Thymic contribution declines further to <1% in older individuals who therefore nearly exclusively rely on peripheral proliferation to repopulate T cells”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Westera et al., 2015
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Immune Checkpoint Inhibitors in the Aged
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Self-citation
- Authors
- Westera, L., van Hoeven, V., Drylewicz, J., Spierenburg, G., van Velzen, J. F., de Boer, R. J., Tesselaar, K., & Borghans, J. A. M.
- Affiliations
- University Medical Center Utrecht (NL)
- Laboratory of Translational Immunology; Department of Immunology; University Medical Center Utrecht; Lundlaan 6 3584 EA Utrecht The Netherlands
- Utrecht University (NL)
- Theoretical Biology and Bioinformatics; Department of Biology; Utrecht University; Padualaan 8 3584 CH Utrecht The Netherlands
- Corresponding author
- Borghans, José A. M.
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2015-01-28
- Volume
- 14
- Issue
- 2
- Pages
- 219-227
- ISSN
- 1474-9718 (ISSN-L)
- PMC
- PMC4364834
- OpenAlex
- W2104316302
- Cited by
- 96
- References
- 50
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 2 · 2023: 11 · 2022: 7 · 2021: 16 · 2020: 4 · 2019: 13 · 2018: 6 · 2017: 9 · 2016: 8 · 2015: 3 · 2013: 1
- FWCI
- 4.26
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Aging Cell (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Funders
- Landsteiner Foundation for Blood Transfusion Research (0812)
- Netherlands Organization for Scientific Research (917.96.350, 836.07.002)
- Virgo consortium (BB.000342.1)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- lymphocyte homeostasis, healthy aging, lymphocyte turnover, thymic output, T cell production, lymphocyte dynamics
- MeSH terms
- Aged, Aging, Deuterium, Female, Flow Cytometry, Homeostasis, Humans, Male, T-Lymphocytes, Water, Young Adult
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