The epigenetic basis of hematopoietic stem cell aging

Highly proliferative tissues such as the gut, skin, and bone marrow lose millions of cells each day to normal attrition and challenge from different biological adversities. To achieve a lifespan beyond the longevity of individual cell types, tissue-specific stem cells sustain these tissues throughout the life of a human. For example, the lifespan of erythrocytes is about 100 days and adults make about two million new erythrocytes every second. A small pool of hematopoietic stem cells (HSCs) in the bone marrow is responsible for the lifetime maintenance of these populations. However, there are changes that occur within the HSC pool during aging. Biologically, these changes manifest as blunted immune responses, decreased bone marrow cellularity, and increased risk of myeloid diseases. Understanding the molecular mechanisms underlying dysfunction of aging HSCs is an important focus of biomedical research. With advances in modern health care, the average age of the general population is ever increasing. If molecular or pharmacological interventions could be discovered that rejuvenate aging HSCs, it could reduce the burden of age related immune system compromise as well as open up new opportunities for treatment of hematological disorders with regenerative therapy.