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Telomere Fluorescence Measurements in Granulocytes and T Lymphocyte Subsets Point to a High Turnover of Hematopoietic Stem Cells and Memory T Cells in Early Childhood
Open accessAbstract
To study telomere length dynamics in hematopoietic cells with age, we analyzed the average length of telomere repeat sequences in diverse populations of nucleated blood cells. More than 500 individuals ranging in age from 0 to 90 yr, including 36 pairs of monozygous and dizygotic twins, were analyzed using quantitative fluorescence in situ hybridization and flow cytometry. Granulocytes and naive T cells showed a parallel biphasic decline in telomere length with age that most likely reflected accumulated cell divisions in the common precursors of both cell types: hematopoietic stem cells. Telomere loss was very rapid in the first year, and continued for more than eight decades at a 30-fold lower rate. Memory T cells also showed an initial rapid decline in telomere length with age. However, in contrast to naive T cells, this decline continued for several years, and in older individuals lymphocytes typically had shorter telomeres than did granulocytes. Our findings point to a dramatic decline in stem cell turnover in early childhood and support the notion that cell divisions in hematopoietic stem cells and T cells result in loss of telomeric DNA.
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“Moreover, TL naive T cells are longer than that of memory T cells [224].”
From Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy (2024) · cites this paper as [224]
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“T‐cell telomere length declines with age (Rufer et al, 1999), suggesting they have undergone replicative senescence from repetitive divisions.”
From The struggle of a good friend getting old: cellular senescence in viral responses and therapy (2021) · cites this paper as Rufer et al, 1999
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“When examining telomere measurements within a mixed cell population, it is important to note that this is a surrogate marker of the mean in a heterogeneous cell population and that telomere length is mosaic, reflecting the telomere length regulation and replicative history of each cell type51,52.”
From The telomere syndromes (2012) · cites this paper as [52]
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Metadata
- Authors
- Rufer, N., Brümmendorf, T. H., Kolvraa, S., Bischoff, C., Christensen, K., Wadsworth, L., Schulzer, M., & Lansdorp, P. M.
- Affiliations
- aFrom the Terry Fox Laboratory, British Columbia Cancer Research Centre, Vancouver, British Columbia V5Z 1L3, Canada
- bInstitute of Human Genetics, University of Aarhus, 8000 Aarhus, Denmark
- Aarhus University (DK)
- University of Southern Denmark (DK)
- University of British Columbia (CA)
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 1999-07-19
- Volume
- 190
- Issue
- 2
- Pages
- 157-168
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2195579
- OpenAlex
- W2064651531
- Cited by
- 709
- References
- 53
- Citations by year
- 2026: 8 · 2025: 8 · 2024: 17 · 2023: 21 · 2022: 45 · 2021: 24 · 2020: 17 · 2019: 18 · 2018: 25 · 2017: 21 · 2016: 16 · 2015: 30 · 2014: 21 · 2013: 19 · 2012: 31
- FWCI
- 18.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- SERVAL (Université de Lausanne) (publishedVersion, cc-by-nc-sa)
- IRIS (submittedVersion, cc-by-nc-sa)
- University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion)
- Funders
- National Research Foundation
- Deutsche Forschungsgemeinschaft
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Danmarks Grundforskningsfond (PO1-AG08761)
- National Institutes of Health (1r01gm056162-01)
- National Institute on Aging (PO1-AG08761, NIA-PO1-AG08761, P01AG008761)
- National Cancer Institute
- National Institute of General Medical Sciences (GM56162)
- National Institute of Allergy and Infectious Diseases (AI 29524, R21AI029524, R01AI029524)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- telomere length, hematopoietic stem cells, memory T cells, naive T cells, granulocytes, aging, cell division, early childhood, telomere shortening
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Aging, Child, Child, Preschool, Female, Flow Cytometry, Granulocytes, Hematopoietic Stem Cells, Humans, Immunologic Memory, Infant, Infant, Newborn, Male, Middle Aged, Twins, Dizygotic, Twins, Monozygotic, T-Lymphocyte Subsets, Telomere, In Situ Hybridization, Fluorescence, Terminal Repeat Sequences
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