Fight Aging!

SkQ1 is a mitochondrially targeted antioxidant, and there is evidence to show that it can modestly extend life in mice. Mitochondria are important in the aging process, and one of the ways in which they interact with surrounding cell biology is by generating damaging reactive oxygen species (ROS). Too much ROS creation can harm a cell, a state called oxidative stress. Just a little more than usual can be beneficial, as the cell reacts with increased housekeeping for a net benefit - this is probably one of the mechanisms by which exercise improves health, for example.

This signaling is a parallel mechanism to the most important harm likely caused by mitochondrial ROS, however, which is to damage mitochondrial DNA at their point of origin. This can lead to all sorts of persistent dysfunction in a small population of cells, which export harmful molecules to surrounding tissues. Mitochondrial antioxidants probably produce benefits to long term health by reducing the rate of this mitochondrial damage, but that isn't completely certain at this point because of the ROS signaling to other important aspects of cell metabolism. Biology is complex, and as for all small effects on longevity, the actual mechanism could be any one of a number of things.

So these researchers are making use of SkQ1 as a way to better identify what exactly it is that changes in response to ROS levels, with a focus on dysfunction in blood vessel wall tissue (the vascular endothelium) that leads to age-related conditions such as atherosclerosis:

Cardiovascular diseases (CVDs) have a great impact in morbidity and mortality all over the world. One of the major risk factors for development of CVDs is aging. In recent years a vast amount of information has been obtained pointing to a crucial role of endothelium in the development of age-related CVDs. A healthy endothelium fulfils numerous functions in vascular biology including inflammatory responses, as well as vascular tone and permeability. Endothelial dysfunction is typical for many pathological conditions including atherosclerosis, type I and II diabetes, inflammatory processes, and aging. Aging is associated with increased oxidative stress and a proinflammatory endothelial cell phenotype. Excessive or prolonged endothelium activation due to the action of the proinflammatory cytokines underlies endothelium dysfunction.

The "inflammaging theory" postulates that aging phenotype can be explained by an imbalance between inflammatory and antiinflammatory networks, which results in low-grade chronic proinflammatory status. The inflammatory vascular reactions are mediated by complex interactions between circulating leukocytes and the endothelium. Proinflammatory cytokines including TNF increase expression of cell adhesion molecules (CAMs) and leukocyte adhesion followed by invasion through the vascular endothelium.

We have shown that old mice have increased levels of the vascular inflammatory markers in plasma (TNF and IL-6) and in aorta tissues (ICAM1, VCAM, TNF, and MCP1). A significant body of evidence indicates that mitochondrial dysfunction and excessive mtROS production are involved in vascular inflammation and age-related CVDs. Long-term administration of the mitochondria-targeted antioxidant SkQ1 to old mice completely prevented the age-related increase in aortic ICAM1 mRNA expression and attenuated the increase in expression of the other proinflammatory genes. However, SkQ1 did not affect circulatory TNF and IL-6 levels, thus indicating that mtROS are critical for inflammatory signaling downstream from cytokine expression.

Increased expression of CAMs is implicated in early steps of atherosclerosis. The suppression of leukocyte adhesion to endothelial cells by reducing CAM expression prevented development of atherosclerosis and had positive effects on many aseptic inflammatory pathologies. According to our data, mtROS scavenging may attenuate age-related increase in CAM expression and related endothelial dysfunction.

Link: http://www.impactaging.com/papers/v6/n8/full/100685.html