PROJECT SUMMARY

Mutations or errors in the DNA in blood cells occur with increasing frequency with aging. When blood cells acquire these mutations without any evidence of blood cancer development, this state is termed clonal hematopoiesis. Recent studies suggest that the presence of clonal hematopoiesis increases the risk of cardiovascular disease in aging individuals because of increased inflammation and that these individuals with clonal hematopoiesis have an elevated risk of developing blood cancers. Whether clonal hematopoiesis influences other conditions associated with aging is unknown. We previously discovered that individuals with clonal hematopoiesis have an elevated risk of bone loss, and seek to define the inflammatory signals that are involved in this process. Using mouse models of the most common mutation in clonal hematopoiesis, I seek to inhibit these inflammatory signals to determine whether it resolves the inflammatory consequences on clonal hematopoiesis including bone loss. This will pave the way for the development of therapeutics to treat inflammatory conditions related to clonal hematopoiesis.