New insights on aging: Location is crucial in determining if reactive oxygen species are beneficial or detrimental

GRAND RAPIDS, Mich. (February 11, 2015) — Using antioxidants to combat the effects of aging may only be beneficial if the treatment is targeted to specific areas in a cell, according to recent work by Van Andel Research Institute (VARI) scientists.

Investigators in VARI’s Laboratory of Aging and Neurodegenerative Disease, led by Jeremy Van Raamsdonk, Ph.D., have shown that reactive oxygen species (ROS) can have opposite effects on aging depending on where the ROS are located— increased levels of ROS in the cytoplasm decreases lifespan in the worm Caenorhabditis elegans while increased levels of ROS in the mitochondria of cells increases lifespan. Taken with Van Raamsdonk’s previous work, this study shows the complex relationship between ROS and lifespan, which is determined by where ROS are located in the cell and how much ROS is present. The study, Mitochondrial and cytoplasmic ROS have opposing effects on lifespan, will be published February 11 in PLoS Genetics.

The research provides novel insights into the free radical theory of aging, which suggests that ROS created by normal metabolic processes cause damage that accumulates over time to cause aging. An increase in oxidative damage caused by ROS may also contribute to the development of neurodegenerative diseases. In recent years, molecules that detoxify ROS called antioxidants have become a popular method for combating the effects of aging and are an important focus area for research into the prevention of neurodegenerative diseases and other conditions.

“This work shows that the relationship between ROS and aging is not simple,” Van Raamsdonk said. “ROS are neither good nor bad. They have functional roles in the cell and it appears that it is crucial to have the right levels of ROS in the right location. This means that treatments with antioxidants may need to be targeted to maximize beneficial effects and minimize possible detrimental effects.”

Van Raamsdonk and his team used a genetic approach to specifically increase the levels of ROS in different parts of the cell by decreasing the expression of an antioxidant enzyme called superoxide dismutase, which acts to eliminate ROS. In order to increase the possibility of observing a difference, they also utilized a mutant worm model that has increased sensitivity to ROS. Using this approach, they were able to show that increasing ROS in the mitochondria increased lifespan, while increasing ROS in other parts of the cell either had no effect or decreased lifespan.

Knowing how the location and levels of ROS impact longevity will allow scientists to better target antioxidant treatments to those areas where certain ROS levels are detrimental. Additionally, it provides a roadmap to areas where antioxidant treatments may cause negative effects and should be avoided. Future work will need to further define the functional roles of ROS and how elevated ROS can prolong lifespan. This knowledge may eventually be used to promote longevity and understand the role of ROS in age-related conditions where free radical stress seems to play a part, such as Parkinson’s disease.

ABOUT VAN ANDEL INSTITUTE

Van Andel Institute (VAI) is an independent biomedical research and science education organization committed to improving the health and enhancing the lives of current and future generations. Established by Jay and Betty Van Andel in 1996, VAI is based in Grand Rapids, Michigan. Van Andel Research Institute (VARI), VAI’s research division, is dedicated to determining the epigenetic, genetic, molecular and cellular origins of cancer, Parkinson’s and other diseases and working to translate those findings into effective therapies. More than 270 scientists and support staff work in on-site laboratories and in collaborative partnerships that span the globe. Find out more about Van Andel Institute or donate by visiting www.vai.org. 100% To Research, Discovery & Hope®