An encouraging new study has demonstrated that a mitochondria-targeted antioxidant compound may be able to reverse some of the effects of aging on vascular function, which scientists believe could ultimately serve as a promising strategy in the prevention of age-related cardiovascular disease. The study has been published in The Journal of Physiology.
Aging is the primary risk factor for the development of cardiovascular disease (CVD). When we age the layer of cells lining our arteries, called the endothelium, begins to decline in function. The endothelium plays a critical role in the dilation and constriction of blood vessels, but as we get older it becomes impaired in its ability to trigger dilation; it is this endothelial dysfunction that is a major driving force in the development of CVD.
One of the molecules involved in regulating blood flow by triggering arterial dilation is the highly reactive signaling molecule nitric oxide (NO), which is naturally produced by the body. As we age our cellular energy-making factories, called mitochondria, produce increasing amounts of reactive oxygen species (ROS), namely superoxide, which react with NO and reduce its availability. The product of this reaction also inactivates a molecule involved in the synthesis of NO, further decreasing the amount of NO available.
Superoxide might sound bad, but it’s actually important in the maintenance of numerous cellular functions, and usually it’s maintained at safe levels by our own antioxidant molecules. “You have this kind of balance, but with aging there is this shift,” said lead-author of the study Rachel Gioscia-Ryan in a press-release. “There become way more reactive oxygen species than your antioxidant defenses can handle.”
This process is known as oxidative stress, which is a hallmark of mitochondrial dysfunction. Prior to this study it was unknown as to whether oxidative stress in the mitochondria of endothelial cells contributed to the age-related decline of vascular function.
In order to investigate this scientists from the University of Colorado Boulder supplied old mice (the equivalent of 70- to 80-year-old humans) with an antioxidant molecule called MitoQ for four weeks. MitoQ is a modified form of the naturally occurring antioxidant ubiquinone which has a positively charged molecule attached to it. It is the addition of this molecule that specifically targets MitoQ to the mitochondria. Previous studies using antioxidant therapy have shown few beneficial effects on vascular function, probably because they weren’t successfully getting to the mitochondria.
The team found that MitoQ not only increased the amount of NO available, it also improved the health of the vascular mitochondria and reduced mitochondrial oxidative stress. Perhaps more importantly the study found that the MitoQ successfully reversed the age-related vascular endothelial dysfunction in these mice; after treatment the arteries functioned as well as those found in young adult mice.
These results suggest that MitoQ may be a promising strategy to preserve vascular endothelial function in aging, which could help to prevent the onset of age-related CVD. What’s also encouraging about the prospects of this study is that MitoQ is not a novel drug; it’s already been used in human Phase II clinical trials and was found to be well tolerated.