The hallmarks of aging in skeletal muscle include endothelial cell dysfunction, impaired microcapillary formation, and a progressive decline in exercise capacity, yet the underlying causes of these symptoms are poorly understood. In a recent paper, researchers identify the mechanism behind vascular aging in mice and its effects on muscle health, and show the means by which they successfully reversed the process in animals.

The vascular aging process causes us to suffer from disorders such as cardiac and neurologic conditions, muscle loss, impaired wound healing, and overall frailty. As we age, our tiniest blood vessels wither and die, causing reduced blood flow and compromised oxygenation of organs and tissues. Endothelial cells are essential for the health and growth of the blood vessels that they line. Unfortunately, as these endothelial cells age, blood vessels deteriorate, new blood vessels fail to form, and blood flow to most parts of the body gradually diminishes. This process heavily affects the muscles, which are vascularized and rely on a robust blood supply to function. Exercise can slow the process, but over time, it becomes less effective.

The research team found that reduced blood flow develops as endothelial cells start to lose a critical protein known as SIRT1, which has been known to delay aging and extend life in yeast and mice. SIRT1 loss is precipitated by the loss of NAD+, a key regulator of protein interactions and DNA repair. Through a series of experiments, researchers found that NAD++ and SIRT1 provide a signaling network between endothelial cells in the walls of blood vessels and muscle cells, thus generating new capillaries to supply oxygen and nutrients to tissues and organs. By using an NAD++ precursor treatment in aging mice, the scientists saw a boost in the number of blood capillaries and capillary density, increasing the blood flow to muscles. These findings have implications for improving blood flow, increasing human performance, and reestablishing a cycle of mobility in the elderly, paving the way for therapies to address diseases that arise from vascular aging.