FOXOs and Sirtuins in Vascular Growth, Maintenance, and Aging

Blood vessels form the first organ in the developing embryo and build extensive networks that supply all cells with nutrients and oxygen throughout life. As blood vessels get older, they often become abnormal in structure and function, thereby contributing to numerous age-associated diseases including ischemic heart and brain disease, neurodegeneration, or cancer. First described as regulators of the aging process in invertebrate model organisms, Forkhead box O (FOXO) transcription factors and sirtuin deacetylases are now emerging as key regulators of mammalian vascular development and disease. The integration of individual FOXO and sirtuin family members into various aspects of vessel growth, maintenance, and function provides new perspectives on disease mechanisms of aging, the most important risk factor for medical maladies of the vascular system. (Circ Res. 2012;110:1238-1251.)