Submitted January 24, 2007
Accepted October 9, 2007
Effects of dietary restriction on hematopoietic
stem cell aging are genetically regulated
Robin P. Ertl, Jichun Chen, Clinton M. Astle, Theodore M. Duffy, and David E. Harrison*
The Jackson Laboratory, Bar Harbor, ME, United States
Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, United States
* Corresponding author; email: david.harrison{at}jax.org.
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 is due to 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 neither affected 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. The fact that DR increases or maintains stem cell function with age, while decreasing cancer, has far-reaching health implications.
