Changes in Bone Marrow

The percentage of marrow space occupied by hematopoietic tissue declines progressively from birth until about age 30, when it levels off. After about age 70, it again declines progressively, starting with the long bones, especially the femur; the flat bones are relatively spared. Whether the second decline results from an intrinsic reduction in blood-forming elements or from an increase in bone marrow fat displacing hematologic tissue is not known.

Several age-related changes occur in marrow function. The number of stem cells in marrow decreases significantly with age, although the length of time that marrow can be maintained in tissue culture by serial transplantation is the same for elderly and younger adults. The rate of incorporation of iron in marrow culture is comparable in elderly and younger adults, but in the elderly, the rate increases less with erythropoietin stimulation. Iron uptake from the intestines is normal in the elderly, but slowed erythropoiesis reduces incorporation of iron into red blood cells (RBCs). Clonal hematopoiesis, resulting from oncogene mutations, has been observed in healthy elderly persons without morphologic or functional hematologic abnormalities.

In animal studies, healthy older subjects are unable to produce reticulocytes in response to hemorrhage or hypoxemia as efficiently as younger subjects. Whether this defect is due to ineffective erythropoiesis, to changes in the hematopoietic elements, to a decrease in growth factors, or to age-related architectural changes in the marrow is unclear. In elderly patients, such findings (slow recovery of peripheral hematologic values after hemorrhage or severe infection) are termed decreased marrow reserve. However, some studies suggest that the response to hemorrhage in the elderly is just as effective as that in younger adults and that hematopoietic response to administered growth factors (eg, erythropoietin, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interleukin-3) is well maintained in the elderly.

These changes in marrow function are not secondary to nutritional deficiencies, because total body iron and bone marrow iron increase with age, and folate and vitamin B₁₂ levels in healthy elderly persons remain within the normal range.