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

doi:10.1016/S0047-6374(00)00137-8

Mechanisms of Ageing and Development

Volume 117, Issues 1–3, 15 August 2000, Pages 57-68

https://doi.org/10.1016/S0047-6374(00)00137-8 Get rights and content

Abstract

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.

Introduction

Bone marrow is a primary source of various kinds of blood cells and, thus, is frequently used for diagnosis of various diseases as well as evaluation of therapeutic agents. Therefore, knowledge of the normal variations with aging of the bone marrow is essential for the interpretation of the change of bone marrow features. Although there is an apparent age-related decrease in the amount of hematopoietic tissue in the human bone marrow (Hartsock et al., 1965), the mechanisms that regulate age-related change of bone marrow hematopoiesis are still unclear. Furthermore, age change of hematopoiesis is not commonly seen in mammals: For example, the age-related decrease in the amount of bone marrow parenchyma is observed in humans and rats but not in mice.

In human bone marrow, erythropoietic progenitor decreases with age, when measured by CFU-E (Lipschitz et al., 1984). There is no age-related change in the proportion of CD34-positive marrow cells, but the sensitivity of progenitors from the elderly to growth factors decreases 2-fold as compared with those from young adults (Chatta et al., 1993). Bone marrow CD34-positive cells generate fewer T cells in vitro with increasing age, especially following chemotherapy (Offner et al., 1999). An age-related increase of plasma cells (IgG and IgA) is observed with a concomitant increase of these immunoglobulins in the serum (Suzuki et al., 1984).

In animal experiments, progenitors of both T cells and B cells decrease with age (Tyan, 1977, Hirokawa et al., 1986, Jonsson and Philips, 1993). Williams et al. (1986) examined aged C57BL/6 mice and reported that basal hematopoiesis was unaltered by aging, although the bone marrow reserve capacity was markedly compromised.

Various types of cells and multiple regulatory factors of the bone marrow, the so-called microenvironment, would be important for supporting and maintaining hematopoiesis in the bone marrow. Some specific stromal cells, such as ST2 (Ogawa et al., 1988), and nonspecific cognate reaction among various cells are considered to play an important role in normal hematopoiesis. The latter includes relatively minor cell components such as T cells, B cells and macrophages, although fibroblasts, endothelial cells and adipose cells may also affect hematopoiesis in the bone marrow. For instance, macrophages may play a role in the maintenance of normal hematopoiesis, since abnormal behavior of macrophages appears to be responsible for inducing ineffective hematopoiesis in myelodysplastic syndromes (Kitagawa et al., 1998) and for inducing myelopoiesis in myeloproliferative disorders (Sadahira et al., 1999) in humans. In the present study, we first focused on the age-related changes of bone marrow cellularity, proliferating activity/apoptotic features of hematopoietic cells. The changes affecting the microenvironment were then determined by estimating numbers of T cells, B cells and macrophages in human bone marrow, obtained from people not suffering from any specific hematological diseases.

Section snippets

Bone marrow materials

Bone marrow samples of trephin biopsy were obtained from 100 patients who have not been suffering from hematological disorders. Samples were taken from the sternal bone or, in some cases, the iliac crest. Age and sex distributions of these patients are listed in Table 1. Some patients were undergoing staging for solid tumors, some were donors for bone marrow transplantation, and others had mild anemia, mild thrombocytopenia, fever of unknown origin, diabetes mellitus, liver cirrhosis, or

Cellularity of the bone marrow

The cellularities of the bone marrow samples examined in the present study are presented in Table 1. They ranged between 40 and 60 in most cases from the second to the eighth decade, and there was no definite age-related change. However, it was important to note that the lowest cellularity was seen in the oldest group ranging in age from 80 to 100 years. The difference was significant between the cellularity of oldest group and that of patients in the first to the eighth decade (P<0.01).

Ki-67-positive cells in the bone marrow (Fig. 1A–C and Fig. 2)

The

Discussion

The amount of hematopoietic tissue in bone marrow of humans is known to decrease with age, gradually being replaced by fatty tissue. In the elderly people, the fatty replacement was most commonly observed in femoral bone, and also sporadically in vertebral and sternal bone (Custer and Ahlfeldt, 1932). Using necropsy samples from the anterior iliac crest, Hartsock et al. (1965) have reported the variations of the mean percentage of hematopoietic tissue in bone marrow with aging. The initial

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

Abstract

Introduction

Section snippets

Bone marrow materials

Cellularity of the bone marrow

Ki-67-positive cells in the bone marrow (Fig. 1A–C and Fig. 2)

Discussion

Blood

Blood

Cell. Immunol.

Cell. Immunol.

Blood

Blood

Blood

Murine macrophages express abundant insulin-like growth factor-I class I Ea and Eb transcripts

Endocrinology

Hematopoietic progenitors and aging: alterations in granulocytic precursors and responsiveness to recombinant human G-CSF, GM-CSF, and IL3

J. Gerontol.

Studies on structure and function of bone marrow. II. Variations in cellularity in various bones with advancing years of life and their relative response to stimuli

J. Lab. Clin. Med.

Normal variations with aging of the amount of hematopoietic tissue in bone marrow from the anterior iliac crest

Am. J. Clin. Pathol.

Growth hormone, growth factors and hematopoiesis

Horm. Res.

Increase in number of bone marrow macrophages in patients with myelodysplastic syndromes

Eur. J. Haematol.