The cellular and molecular basis of age-dependent anemia: a single cell-based approach

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As we age our ability to produce the red blood cells that transport oxygen within the body declines, leading to increasing prevalence of anemia (i.e. low red cell mass) with age. This is accompanied by a higher risk of numerous infirmities associated with old age, including loss of mental capabilities, loss of mobility, as well as increased risk of hospitalization and of death associated with surgical procedures. While in some people the cause of the anemia can be identified as chronic inflammation or kidney dysfunction, about a third have no identifiable cause. In this project we will examine if changes to the hematopoietic stem cells (HSCs), the cells that produce all blood cell types, play a role in age-dependent anemia. We have developed a technique that allows us to measure the red cell production of a single HSC, and found that there are different types of HSCs with vastly different ability to make red blood cells. We now wish to examine if changes to the abundance of the different HSC subtypes can account for the decline in red cell production, and in addition, whether such changes are due to influences from the cells that surround and support the HSCs in the bone marrow.The aim of these studies is to identify mechanisms by which the decline in red cell production can be prevented, or ultimately reverted.