Grant: Operating Grant

We are studying the multiple functions of co-enzyme Q (CoQ; CoQ10) in health and disease, and how these functions relate to the aging process. Co-enzyme Q, which is also known as "ubiquinone", has many important functions in the cell, in particular in the mitochondria, the organelle in which cellular energy is produced. Even partial deficiencies in the levels of CoQ lead to severe disease in people. In the mitochondria, CoQ is needed for energy production and is involved both in the production and in the elimination of free radicals (also known as reactive oxygen species). During the aging process there is a gradual loss of mitochondrial function and an increase in free radical levels but the exact role of either process remains controversial. CoQ is used as a health supplement and as an anti-aging compound because of its known function in eliminating free radicals. However, it is not well established whether consuming CoQ is really beneficial and, if it is, for what reason. We have created mutant mice which lose the CoQ content of their cells only very slowly and very gradually, which leads to low body weight and a shortened lifespan. We have also found a way to stabilize the loss, so that we can obtain animals that contain different levels of CoQ without further loss. By studying these animals, as well as their mitochondria, cells, and organs at different time points after the animals begin to lose CoQ and in animals in which the loss has been stabilized, we can determine how the level of CoQ is related to different biochemical, cellular and whole animal parameters, including how much energy and free radicals the mitochondria produce, and how this affects the aging process. The understanding that we will gain will help to better understand how loss of CoQ leads to disease, in which situation CoQ supplementation might be beneficial, and more generally how mitochondrial function and free radicals determine cellular health and thus affect the aging process.