High rate of leukemia in elderly may be due to stem cell aging

Hematopoietic stem cells (HSCs) from healthy persons older than 65 years make fewer immunoprotective lymphocytes than do stem cells from healthy persons aged 20 to 35 years, and tend to be biased toward producing more myeloid cells. The results suggest that human HSCs struggle as a person ages, and this struggle can sometimes lead to inadequate immune responses as well as the growth of acute myeloid leukemia and other blood cancers.

This finding may explain why older people are more likely than younger people to develop myeloid malignancies and be more vulnerable to infections such as rhinoviruses and influenza, according to a study by Wendy W. Pang, MD, of Stanford University Medical Center in Stanford, California, and colleagues, published in Proceedings of the National Academy of Sciences (www.pnas.org/content/early/2011/11/23/1116110108.full.pdf+html).

Previous studies had shown that in mice, HSCs change in number and function as the mouse grows older. In the current project, Pang's team compared HSC prevalence, distribution, and cell cycle profile in 15 healthy elderly and 28 healthy young people. They learned the following:

  • HSCs comprised a greater proportion of bone marrow cells in persons 65 years and older than in those aged 20 to 35 years.
  • HSCs in the elderly were more likely to be actively dividing than HSCs in the younger participants; however, despite their proliferation, older HSCs were inefficient in keeping up with the body's demands.
  • The older HSCs were less able to differentiate into B lymphocytes and more likely to become myeloid cells.
  • Immunodeficient mice that received older, human HSCs exhibited a higher proportion of myeloid-to-lymphoid cells in their bone marrow weeks to months posttransplant.

The researchers also found that compared with HSCs from people aged 42 to 61 years, HSCs from donors 65 years and older expressed higher levels of several age-related genes associated with the cell cycle, proliferation, and development, as well as genes associated with DNA repair and cell death. The higher level of these genes suggests that the HSCs are entering the cell cycle inappropriately rather than waiting until new blood or immune cells are needed.

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