Abstract: The described invention provides a method for rejuvenating an aging blood and vascular system comprising aging-associated hematopoietic defects in an aging hematopoietic microenvironment of bone marrow including deteriorating vascular integrity, reduced hematopoietic stem cell function, or both. The method includes administering to a subject a pharmaceutical composition comprising an inhibitor of a pro-aging angiocrine factor, a splice variant, or a fragment thereof, and a pharmaceutically acceptable carrier. The described invention has identified thrombospondin-1 as a candidate pro-aging factor.