Bone Marrow Of Aged Mice Research Articles

Quantitative analysis of bone marrow thymic progenitors in young and aged mice

Our studies on the capacity of bone marrow (BM) to generate T lymphocytes in aging have revealed that under the competitive conditions of thymic reconstitution, cells of aged mice are significantly inferior to those of the young. The present study was designed to further investigate the basis of this age-related change. Two mechanisms were considered: (a) The potential of BM-derived T cell precursors from aged mice to proliferate and differentiate in the thymic microenvironment is impaired. (b) The frequency of T cell precursors is reduced in BM of aged mice, thus affecting their ability to compete efficiently in reconstituting the thymus. These possibilities were studied in vitro by colonizing thymocyte-depleted fetal thymic lobes with BM cells from aged (24-month) and young (3-month) C57BL/6 mice. By determining the cell cycle duration of BM-derived cells which have seeded the thymic lobes, we found that cells originating from aged mice proliferate in the thymus at the same rate as those from young mice. Reconstitution with limiting numbers of BM cells indicated that the frequency of thymic progenitors in the BM is significantly reduced in aged as compared to young mice. We thus conclude that aging is associated with a quantitative reduction in the frequency of thymic progenitors in the BM.

Alterations of cell cycle distribution in the bone marrow of aging mice measured by flow cytometry

The effect of aging on the cell cycle distribution in bone marrow cells was measured by flow cytometry with special reference to the lability in bone marrow physiology. Female C3H mice were examined every 3 h during a 24-h period at the age of 16, 21 and 26 months, vs 3-month-old control mice. Considerable circadian fluctuations were found in the different cell cycle phases in young mice. The rhythmicity patterns were different when comparing different months. In aging mice the variations were dampened, while consistent age-related phase shifts were not seen. The maximal 24-h mean numbers of cells in all three cell phases, but especially the S and G 2 phases were reached at 21 months. The relative number of S and G 2 phases were significantly reduced in 26-month-old mice, indicating an age-related shift of the proliferative capacity. The present findings are discussed in relation to age-related changes in granulopoiesis and the increase of myelotoxic effects during cancer chemotherapy in aging individuals.

The frequency and fine specificity of B cells responsive to (4-hydroxy-3-nitrophenyl)acetyl in aged mice

The B-cell response to NP-Hy of two murine strains has been analyzed in order to evaluate the affects of aging on B-cell repertoire expression. The results indicate that for both BALB/c mice (Igh a) and B10.D2 mice (Igh b) the frequency of (4-hydroxy-3-nitrophenyl)acetyl (NP)-responsive splenic B cells is approximately twofold lower, on a per B cell basis, in aged mice as compared to young adults. However, as with previous assessments of the response to DNP-Hy in aged mice, the frequency of newly generated surface immunoglobulin negative bone marrow precursor cells specific for NP in aged BALB/c mice is the same as in young mice. The decrease in frequency of responsive splenic B cells is not accompanied by a measurable decrease in repertoire diversity or changes in clonotype distribution as assessed by (a) representation of κ vs λ light chain-bearing antibodies, (b) binding of monoclonal antibodies to a panel of analogues of NP, and (c) the proportionate representation of B10.D2 monoclonal antibodies that bear NP d idiotypic determinants. By these criteria it appears that down-regulation of B cells as they mature and emerge from the bone marrow of aged mice is pan-specific and does not disproportionately affect B cells of a predominant clonotype family. Consistent with other investigations which have demonstrated differences in secreted antibodies of immunized aged vs young mice, we have observed that 4 weeks after immunization of B10.D2 mice with NP-BSA, the frequency of newly generated secondary B cells is lower in aged than in young mice and the generation of λ-bearing secondary precursor cells is particularly low. Thus, clonotype-specific down-regulation may play a role in shaping the B-cell repertoire subsequent to immunization of aged mice.