Grant: Project Grant

Blood stem cells create all the cells in the circulating blood system, and are also able to generate new stem cells. As an individual gets older, their blood stem cells do not replenish themselves as well. The stem cells also tend to become more of one type of white blood cell while not producing as many immune cells. This combination leads to more inflammation and inflammation-related diseases and less ability to fight infections. microRNAs are small molecules that regulate the function of genes. A single microRNA can regulate the function of many genes. We have found that one of these microRNAs, called miR-146a, decreases with age. Loss of miR-146a results in blood stem cells that do not function as well and resemble the aging stem cell. In part this is because miR-146a regulates genes that drive inflammation. Loss of this microRNA results in continued low level inflammation that we predict results in aging. In this grant, we will examine how miR-146a affects blood stem cell aging with a focus on the inflammatory molecules that it regulates in both mouse and human models. We will also determine whether we can reverse the poor function of old blood stem cells by replenishing miR-146a or blocking inflammation. Because the blood system produces many inflammation-related cells and molecules, and because blood travels all over the body, it is likely that by reversing the aging of blood stem cells that we might also help to reduce the impact of aging on other systems such as the heart and brain.