Age-related changes of human bone marrow: a histometric estimation of proliferative cells, apoptotic cells, T cells, B cells and macrophages

We performed an immunohistological study using biopsy samples of bone marrow obtained from patients, ranging in age from a newborn baby to 100 years old. Those patients suffering from hematological diseases or diseases that would be capable of affecting hematopoiesis were not included in the present study. The cellularity of the bone marrow did not change significantly with age during the first and the eighth decades, while the oldest group, ranging in age from 80 to 100, revealed significantly low cellularity. Proliferative activity assessed by Ki-67-positive cells was high in the middle-aged group and declined slightly in the elderly group. It was of interest to note that the percentage of apoptosis was relatively low in the young and middle-aged group, but significantly increased in the elderly group. The percentage of T cells did not change greatly between the first and the fifth decades, peaked at the sixth decade and gradually decreased thereafter. The percentage of B cells was about 10% at the first decade, decreased thereafter until the third decade, then increased again showing a peak at the sixth decade, and decreased thereafter. The percentage of CD68-positive cells was high in young patients, and decreased in the adult and elderly patients. The data in the present study suggest that hypocellularity in the bone marrow of elderly people could be ascribed partly to the increase of apoptosis, and might possibly be related to a decrease in the number of lymphocytes and macrophages, which would constitute part of the bone marrow microenvironment supporting hematopoiesis.

[1]  S. Arkins,et al.  Murine macrophages express abundant insulin-like growth factor-I class I Ea and Eb transcripts. , 1993, Endocrinology.

[2]  S. R. Viana,et al.  Age-related changes of lymphocyte subsets in normal bone marrow biopsies. , 1998, Cytometry.

[3]  K. Hirokawa,et al.  Localization of Fas and Fas ligand in bone marrow cells demonstrating myelodysplasia , 1998, Leukemia.

[4]  K. Hirokawa,et al.  Expression of inducible nitric oxide synthase (NOS) in bone marrow cells of myelodysplastic syndromes , 1999, Leukemia.

[5]  G. de Haan,et al.  Mouse strain-dependent changes in frequency and proliferation of hematopoietic stem cells during aging: correlation between lifespan and cycling activity. , 1997, Blood.

[6]  K. Hirokawa,et al.  Overexpression of tumor necrosis factor (TNF)-α and interferon (IFN)-γ by bone marrow cells from patients with myelodysplastic syndromes , 1997, Leukemia.

[7]  D. Metcalf.  The molecular biology and functions of the granulocyte-macrophage colony-stimulating factors. , 1986, Blood.

[8]  M. Tyan.  Age-related decrease in mouse T cell progenitors. , 1977, Journal of immunology.

[9]  K. Hirokawa,et al.  Age-related change in the potential of bone marrow cells to repopulate the thymus and splenic T cells in mice. , 1986, Cellular immunology.

[10]  J. Jönsson,et al.  Interleukin-7 responsiveness of B220+ B cell precursors from bone marrow decreases in aging mice. , 1993, Cellular immunology.

[11]  J. Nemunaitis,et al.  Regulation of cytokine and growth factor gene expression in human bone marrow stromal cells transformed with simian virus 40. , 1990, Blood.

[12]  F. Offner,et al.  Bone marrow CD34+ cells generate fewer T cells in vitro with increasing age and following chemotherapy , 1999, British journal of haematology.

[13]  K. Kaushansky,et al.  Interleukin-1 alpha also induces granulocyte-macrophage colony-stimulating factor in immature normal bone marrow cells. , 1990, Blood.

[14]  G. Chatta,et al.  Hematopoietic progenitors and aging: alterations in granulocytic precursors and responsiveness to recombinant human G-CSF, GM-CSF, and IL-3. , 1993, Journal of gerontology.

[15]  K. Hirokawa,et al.  Differential age-change in the numbers of CD4+CD45RA+ DC4+CD29+ T cell subsets in human peripheral blood , 1992, Mechanisms of Ageing and Development.

[16]  R. Dantzer,et al.  IL-4 and insulin-like growth factor-I inhibit the decline in Bcl-2 and promote the survival of IL-3-deprived myeloid progenitors. , 1997, Journal of immunology.

[17]  R. Dantzer,et al.  Growth hormone, growth factors and hematopoiesis. , 1996, Hormone research.

[18]  M. Kitagawa,et al.  Increase in number of bone marrow macrophages in patients with myelodysplastic syndromes , 1993, European journal of haematology.

[19]  M. Ogawa,et al.  B cell ontogeny in murine embryo studied by a culture system with the monolayer of a stromal cell clone, ST2: B cell progenitor develops first in the embryonal body rather than in the yolk sac. , 1988, The EMBO journal.

[20]  Josef M. Penninger,et al.  Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand , 1999, Nature.

[21]  Williams Lh,et al.  Evaluation of the effect of age on hematopoiesis in the C57BL/6 mouse. , 1986 .

[22]  T. Manabe,et al.  Immunohistochemical assessment of human bone marrow macrophages in hematologic disorders , 1999, Pathology international.

[23]  K. Udupa,et al.  Effect of age on hematopoiesis in man. , 1984, Blood.

[24]  C S PETTY,et al.  NORMAL VARIATIONS WITH AGING OF THE AMOUNT OF HEMATOPOIETIC TISSUE IN BONE MARROW FROM THE ANTERIOR ILIAC CREST. A STUDY MADE FROM 177 CASES OF SUDDEN DEATH EXAMINED BY NECROPSY. , 1965, American journal of clinical pathology.