Blood

In mammals, the cells of the blood are produced in the bone marrow. Blood cell production depends upon a small population of cells known as hematopoietic stem cells (HSCs). In the bone marrow milieu, these cells can differentiate to give rise to mature cells of any of the eight blood cell lineages. This process, the development of these eight highly specialized cell types from the pluripotent HSC, is called hematopoiesis.

Most mature blood cells are rather short-lived. For example, red blood cells (erythrocytes) survive for three to four months after they are released into the blood from the bone marrow; neutrophils last only about a week. To maintain appropriate numbers of blood cells the bone marrow continuously produces new blood cells—normally about 1 percent of the red blood cells and 10 percent of the granulocytes of the body are replaced each day. Thus, unlike most adult body tissues, which may lose the capacity to undergo cell division (e.g., nerve tissue) or divide only in response to stress (e.g., liver and kidney), the cells of the bone marrow divide actively throughout life; this may have implications for blood homeostasis in aging humans. In the early 1960s, Leonard Hayflick observed that human diploid cells grown in the laboratory could divide only a finite number of times even under optimal conditions. This phenomenon, known as the "Hayflick Limit," is caused in part by erosion of tandem repeat DNA sequences at the telomeres of chromosomes. These sequences are added to the ends of chromosomes by a specific enzyme, telomerase, which is not active in adult cells. Every time a cell divides there is loss of part of the telomeric repeat array, resulting in progressive loss of these sequences and eventually in impairment of essential cell functions. It has been suggested that the requirement for continuous cell division in the bone marrow may therefore result, in older adults, in "exhaustion" of HSCs.

Some observations in humans and in laboratory animals lend support to the notion of HSC exhaustion. The cellularity of the human bone marrow diminishes with increasing age. At birth, 80–100 percent of the marrow is made up of hematopoietic cells, with the balance occupied by fat, whereas in adults younger than sixty-five years the marrow cellularity is approximately 50 percent, further declining to 30 percent by age seventy-five. Furthermore, hemoglobin levels, which indicate the number of circulating red blood cells, are lower, on average, in older adults (see below). In human and mouse bone marrow, hematopoietic progenitor cells from older individuals exhibit reduced capacity to proliferate in vitro. A more physiologic assessment of HSC function may be obtained from transplantation studies. In mice, bone marrow cells from older donors work as well as those from young mice in restoring hematopoiesis in irradiated recipients, while in humans, bone marrow transplants are successfully performed from donors in their seventies. Old HSCs appear, therefore, to be of equal quality to younger ones, insofar as this can be estimated, but to be fewer in number with age. Overall, theoretical considerations combined with the laboratory and clinical data suggest that aging does reduce the proliferative capacity of HSCs. This reduction is too small to be clinically significant under normal circumstances, although it may result in a reduction in the reserve capacity of the marrow, and could account for an increased susceptibility to anemia in older adults.