Dietary restriction improves repopulation but impairs lymphoid differentiation capacity of hematopoietic stem cells in early aging
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Dietary restriction (DR) improves health, delays tissue aging, and elongates survival in flies and worms. However, studies on laboratory mice and nonhuman primates revealed ambiguous effects of DR on lifespan despite improvements in health parameters. In this study, we analyzed consequences of adult-onset DR (24 h to 1 yr) on hematopoietic stem cell (HSC) function. DR ameliorated HSC aging phenotypes, such as the increase in number of HSCs and the skewing toward myeloid-biased HSCs during aging. Furthermore, DR increased HSC quiescence and improved the maintenance of the repopulation capacity of HSCs during aging. In contrast to these beneficial effects, DR strongly impaired HSC differentiation into lymphoid lineages and particularly inhibited the proliferation of lymphoid progenitors, resulting in decreased production of peripheral B lymphocytes and impaired immune function. The study shows that DR-dependent suppression of growth factors and interleukins mediates these divergent effects caused by DR. Supplementation of insulin-like growth factor 1 partially reverted the DR-induced quiescence of HSCs, whereas IL-6/IL-7 substitutions rescued the impairment of B lymphopoiesis exposed to DR. Together, these findings delineate positive and negative effects of long-term DR on HSC functionality involving distinct stress and growth signaling pathways.
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Dietary restriction enhances the repopulating ability of HSCs.
“In the blood, dietary restriction enhances the repopulating ability of HSCs, but also suppresses differentiation along the lymphoid lineage212.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [212]
Dietary restriction suppresses differentiation along the lymphoid lineage.
“In the blood, dietary restriction enhances the repopulating ability of HSCs, but also suppresses differentiation along the lymphoid lineage212.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [212]
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- Authors
- Tang, D., Tao, S., Chen, Z., Koliesnik, I. O., Calmes, P. G., Hoerr, V., Han, B., Gebert, N., Zörnig, M., Löffler, B., Morita, Y., & Rudolph, K. L.
- Affiliations
- Leibniz Institute on Aging - Fritz Lipmann Institute (FLI) (DE)
- Jena University Hospital (DE)
- Georg Speyer Haus (DE)
- Corresponding author
- Morita, Yohei
- Rudolph, Karl Lenhard
- ORCID
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2016-03-07
- Volume
- 213
- Issue
- 4
- Pages
- 535-553
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC4821645
- OpenAlex
- W2294393418
- Cited by
- 133
- References
- 102
- Citations by year
- 2026: 14 · 2025: 10 · 2024: 14 · 2023: 16 · 2022: 13 · 2021: 10 · 2020: 19 · 2019: 13 · 2018: 10 · 2017: 10 · 2016: 4
- FWCI
- 11.73
- Type
- journal article
- Language
- en
- Update notices
- correction (2020-12-17)
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion, cc-by-nc-sa)
- Funders
- Deutsche Forschungsgemeinschaft (Ru745-10, RU-745-12)
- Federal Ministry of Education and Research (GerontoSys–SyStaR 315894)
- Leibniz Association
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Blood disorders and treatments
- Keywords
- dietary restriction, hematopoietic stem cells, HSC aging, HSC quiescence, lymphoid differentiation, B cell development, insulin-like growth factor I, interleukin-6, IL-7, growth factor signaling, immune function, lifespan
- MeSH terms
- Aging, Animals, Cell Differentiation, Hematopoietic Stem Cells, Cellular Senescence, Mice, Knockout, Caloric Restriction, Lymphopoiesis, Mice, Lymphoid Progenitor Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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