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J Exp Med. 2016 Apr 4;213(4):535-53. doi: 10.1084/jem.20151100. Epub 2016 Mar 7.

Dietary restriction improves repopulation but impairs lymphoid differentiation capacity of hematopoietic stem cells in early aging.

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Leibniz Institute on Aging, Fritz Lipmann Institute (FLI), 07745 Jena, Germany.
Institute of Medical Microbiology, Jena University Hospital, 07743 Jena, Germany.
Georg Speyer Haus, Institute for Tumor Biology and Experimental Therapy, 60596 Frankfurt am Main, Germany.
Leibniz Institute on Aging, Fritz Lipmann Institute (FLI), 07745 Jena, Germany
Leibniz Institute on Aging, Fritz Lipmann Institute (FLI), 07745 Jena, Germany Faculty of Medicine, Friedrich Schiller University, 07743 Jena, Germany


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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