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 Blood, 1 February 2008, Vol. 111, No. 3, pp. 1709-1716.
Prepublished online as a Blood First Edition Paper on October 18, 2007; DOI 10.1182/blood-2007-01-069807.

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STEM CELLS IN HEMATOLOGY

Effects of dietary restriction on hematopoietic stem-cell aging are genetically regulated

Robin P. Ertl1, Jichun Chen2, Clinton M. Astle1, Theodore M. Duffy1, and David E. Harrison1

1 Jackson Laboratory, Bar Harbor, ME; and 2 Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health (NIH), Bethesda, MD

Diminished stem-cell functions with age may be a major cause of anemias and other defects. Unfortunately, treatments that increase stem-cell function can also increase the incidence of cancers. Lifelong dietary restriction (DR) is known to decrease spontaneous cancers and lengthen lifespan. This study examines the effect of DR on the ability of bone marrow cells to repopulate irradiated recipients and produce erythrocytes and lymphocytes. In BALB/cByJ (BALB) mice, repopulating abilities decline with age; DR ameliorates this trend. In C57BL/6J (B6) and (BALB x B6) F1 hybrid (F1) mice, repopulating abilities increase with age; DR maintains this increase. Hematopoietic stem cell (HSC) numbers are highly variable in aged BALB mice; however, the observed loss of marrow function results from a major loss in repopulating ability per HSC. DR greatly ameliorates this loss of function with age. In contrast, function per HSC in B6 mice is affected neither by age nor by DR. Thus, DR increases or maintains increased marrow repopulating ability with age in the 3 different genotypes tested, but effects on function per HSC depend on genotype. That DR increases or maintains stem-cell function with age, while decreasing cancer, has far-reaching health implications.


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