As we age, the tiniest blood vessels in our
bodies wither and die, reducing the blood flow to organs and tissues. Vascular aging causes many diseases -- cardiovascular,
neurological, muscle wasting, frailty, and even aging. Here at Harvard Medical School, we've reversed
the process in mice, setting the stage for radical new therapies to help people. The new study has unraveled the cascade of
interactions between blood vessels and muscles. Endothelial cells, which line the walls of
blood vessels, are essential for the health and growth of the vessels. And as endothelial cells age, blood vessels
begin to atrophy and die. Blood flow to many parts of the body diminishes,
organs and tissues begin to function less well. Blood vessel demise hits muscles especially
hard, because muscles rely on a robust blood supply for their function. This process can be slowed down with regular
exercise, but only up to a point. Over time, even exercise fails to stave off
blood vessel demise and muscle loss. The new findings have cracked the mystery
behind this process. As our blood vessels age, they become deaf
to to the signals from exercise muscles. This acutally leads to the muscles shrinking
as we get older, and therefore we're less able to exercise and grow new blood vessels. A vicious cycle indeed. The two key players in the crosstalk between
blood vessels and muscles are a molecule called NAD and a protein called SIRT1. NAD boosts SIRT 1, which in turn enables the
conversation between muscles and blood vessels. But both NAD and SIRT1 decline as we age. They can no longer perform their role as the
interface between muscles and blood vessels. In our new study, we gave mice NMN, a chemical
compound commonly found in the body and previously shown to boost NAD levels, which in turn boosts
SIRT1. These mice had better endothelial function,
blood vessel growth and improved blood supply to their muscles. And what was most striking? These animals’ capacity for exercise improved
dramatically. In fact, the old mice treated with NMN had
up to 80 percent greater exercise capacity, compared with the untreated old mice. These results, I believe, can help millions
of people who have lost their mobility, or simply can no longer exercise, either through
frailty, disability or old age. This sets the stage for new medicines that
will be able to restore blood flow in organs that have lost it, either through a heart
attack, a stroke, or even in patients with dementia.
