New insights on aging: Location is crucial in determining if reactive oxygen species are beneficial or detrimental
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 present. Taken with Van Raamsdonk’s previous work, this research 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, published 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. Van Raamsdonk and his team utilized a genetic approach to specifically increase the levels of ROS in different parts of the cell. Using the worm Caenorhabditis elegans as a model, they decreased the expression of an antioxidant enzyme called superoxide dismutase, which acts to eliminate ROS. Using this approach, they were able to show that increasing ROS in the mitochondria increases lifespan, while increasing ROS in the cytoplasm decreases lifespan.
Knowing how the location and levels of ROS impact longevity will allow scientists to better target antioxidant treatments to those areas where ROS levels are detrimental and to avoid areas where decreasing ROS may cause negative effects. 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, including neurodegenerative diseases such as Parkinson’s disease.
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Mitochondrial and Cytoplasmic ROS Have Opposing Effects on Lifespan, Schaar CE, Dues DJ, Spielbauer KK, Machiela E, Cooper JF, Senchuk M, et al., PLOS Genetics, DOI: 10.1371/journal.pgen.1004972, published 11 February 2015.
JMVR is supported by the Van Andel Research Institute. SH is funded by grants from the Canadian Institutes of Health Research: MOP-114891, MOP-123295 and MOP-97869 as well as by McGill University. CES was supported by the Frederik and Lena Meijer Student Internship Program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
The authors have declared that no competing interests exist.