Rejuvenation of aged hematopoietic stem cells by suppression of bone marrow inflammaging
Blood stem cells reside within the bone marrow and are endowed with the remarkable ability to generate billions of red blood cells, immune cells and platelets every day, a property that underlies the success behind blood stem cell transplantation therapies. As we age, however, blood stem cells become substantially defective and consequently, older adults frequently manifest anemias, elicit sub-optimal immune responses to infections and vaccines, and require longer times to recover following chemotherapy regimens. While defects within aged stem cells have been well defined, the mechanisms that drive the accrual of these defects remain unclear. Dr. Ramalingam's research indicates that inflammation within the aging bone marrow, arising from an increased uptake of fatty acids, plays a critical role in causing age-related blood stem cell defects. The proposal seeks to examine whether blocking fatty acid uptake into the aging marrow is sufficient to prevent inflammation and restore youthful blood stem cell function.