2008 AFAR Research Grant: Aging and the Red Blood Cell: Linking Endothelial and Exercise Dysfunction

Please give a brief summary of your AFAR research project.
In order to regulate blood pressure, our bodies must tightly control blood flow to muscles. A recent idea is that red blood cells (RBCs) release a substance called ATP, which may precisely match blood flow to where oxygen is needed most. Almost nothing is known about how ATP is released in the blood from RBCs, or how its release changes blood flow. What is known is that ATP infusions can mimic the high blood flows to muscles seen during real exercise, and that ATP release from RBCs is reduced from diabetic patients. The purpose of this study is to test whether ATP is an important signal that will control blood flow, and whether this signaling is impaired in older patients due to impaired ATP release. All subjects will exercise and have blood sampled to measure ATP. Subjects will also exercise under low oxygen conditions as this puts added stress on the body's blood flow control systems. Finally, we will remove a small amount of RBCs to test release of ATP under laboratory controlled conditions. These findings may provide important understanding as to why older patients have poor blood flow, poor exercise tolerance, and ultimately very high risk of cardiovascular disease. Results may also provide insight for possible drug treatment options to improve ATP release and actions.

What problems are you addressing and what specific questions will your research seek to answer?
The key problem in older adults is that blood flow to muscles does not reach the high levels needed to sustain work or exercise. This limits the amount of oxygen to muscles and puts added strain on aging hearts. We will study the relationship between ATP in blood and levels of blood flow. We think this relationship is abnormal with aging. We will also test several ideas about what actually causes ATP to be released from red blood cells, and how aging changes that.

What aspects of your project are most interesting from a scientific point of view?
Scientifically, ATP has the potential to be an extremely important signal that can integrate many other signals in the body. By doing this, it may act as a puppetmaster of blood flow, directing it precisely where it is needed to allow muscles to work hard without putting great strain on the heart.

What are the implications of your research for age-related diseases and disorders?
Like the rest of the body, red blood cells age and might lose some functions over time. If we can understand what is going wrong with ATP release from red blood cells, other scientists can develop specific treatments for improving ATP signals. If we can improve ATP release, it is possible that older adults will tolerate exercise/activity much more, which in turn helps with cardiovascular health. Since red blood cells are also important in forming clots, we may gain more understanding as to how to reduce the increased risk of stroke and heart attack in older adults. ATP may help deliver blood flow to the hardest working muscles, thereby delivering more blood sugar to be "burned" and thus reducing the risk of diabetes that is also prevalent in older Americans.

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