Antioxidants May Have Mixed Effect on Aging

Dr. Jeremy Van Raamsdonk Laboratory of Aging and Neurodegenerative Disease (LAND), Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, Michigan, Department of Translational Science and Molecular Medicine, Department of Genetics, Michigan State University, East Lansing, Michigan, Department of Biology, McGill University, Montreal, Quebec, CanadaMedicalResearch.com Interview with:
Dr. Jeremy Van Raamsdon PhD
Laboratory of Aging and Neurodk egenerative Disease (LAND),
Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, Michigan, Deptment of Translational Science and Molecular Medicine, Department of Genetics, Michigan State University, East Lansing, Michigan,Dep. of Biology, McGill University, Montreal, Quebec, Canada

Medical Research: What is the background for this study? What are the main findings?

Dr. Van Raamsdonk : The free radical theory of aging is one of the most widely accepted theories of aging. This theory suggests that reactive oxygen species (ROS), which are also known as free radicals, cause a type of damage, called oxidative damage, that accumulates over time to cause the functional decline associated with aging. ROS have also been proposed to play a role in many diseases including neurodegenerative disorders such as Parkinson’s disease and Huntington’s disease.

However, recent work has demonstrated that ROS are not necessarily detrimental. ROS perform functional roles in the body and thus it is possible to have too little ROS. We previously showed that increasing ROS by decreasing the levels of an antioxidant enzyme called superoxide dismutase (SOD) does not decrease lifespan even when all of the SOD genes are removed. We also showed that in some cases treatment with an antioxidant, such as Vitamin C, can lead to decreased lifespan. This finding is consistent with human clinical trials in which it has not been possible to show a beneficial effect of antioxidants on longevity.

In this paper we further examine the relationship between ROS and aging. We use a simple genetic model organism, the worm Caenorhabditis elegans, which has been used extensively in aging research, to determine how location impacts the effect of ROS on lifespan. We used a genetic approach to increase the levels of ROS in different parts of a cell and found that location is crucial in determining the effect of ROS on lifespan. Mildly increasing the levels of ROS in the mitochondria increases lifespan, while increasing ROS in the cytoplasm has the opposite effect of decreasing lifespan.

Medical Research: What should clinicians and patients take away from your report?

Dr. Van Raamsdonk: I think the take home message is that the relationship between ROS and aging is complex. ROS are neither good nor bad. While high levels of ROS can be toxic, ROS perform functional roles and thus it is also possible to have too little ROS. In addition to levels, the location of ROS in a cell is important in determining whether they will have a beneficial or detrimental effect. These findings have implications for taking antioxidants to reduce ROS. While antioxidants may be beneficial when ROS levels are too high, it is also possible that they will have a detrimental effect if ROS levels are optimal or low. In addition, this work suggests that it may be necessary to target antioxidants to specific locations in a cell to maximize their benefit and minimize the possibility of having a negative impact.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Van Raamsdonk : I think it will be important to continue to define the functional roles of ROS. By defining the mechanism by which elevated mitochondrial ROS increases lifespan, this knowledge may be used to promote healthy aging and longevity. In future studies, the levels and location of ROS must be considered. In this study we have focused on the relationship between ROS and aging. It would be interesting to extend these studies to examine the importance of the location of ROS in a cell in the context of disease.

Citation:

 Mitochondrial and cytoplasmic ROS have opposing effects on lifespan

Claire E. Schaar , Dylan J. Dues , Katie K. Spielbauer , Emily Machiela, Jason F. Cooper, Megan Senchuk, Siegfried Hekimi, M. Van Raamsdonk

 

MedicalResearch.com Interview with:, & Dr. Jeremy Van Raamsdon PhD (2015). Antioxidants May Have Mixed Effect on Aging MedicalResearch.com