Newswise — Bethesda, Md. – Higher levels of antioxidants – particularly manganese antioxidants – could potentially extend one’s lifespan and radiation resistance, according to a new study published on Jan. 11 in mBio by researchers at the Uniformed Services University of the Health Sciences (USU).
Since 1956, Denham Harman’s Free Radical Theory of aging has argued that free radicals shorten life span. This theory has grown stronger over the decades as scientists have demonstrated many biological mechanisms of aging and stress resistance by studying yeast, flies, and mice. Yet, about 15 years ago, a popular model worm Caenorhabditis elegans, or C. elegans for short, rocked this view, when mutant worms lacking powerful antioxidant enzymes lived longer. This led to the surprising view that Denham Harman’s theory might be wrong.
The new study, “Small-Molecule Mn Antioxidants in Caenorhabditis elegans and Deinococcus radiodurans Supplant MnSOD Enzymes during Aging and Irradiation,” removes the C. elegans aging paradox by showing that the worms accumulate massive quantities of small-molecule manganese (Mn) antioxidant complexes, just like the famously radiation-resistant bacterium Deinococcus radiodurans. As it turns out, these high levels of Mn antioxidants in C. elegans worms can substitute for major antioxidant enzymes, thereby increasing their lifespan even as they grow under intense gamma radiation.
The study’s lead author, Dr. Michael Daly, professor of Pathology at USU, explains that the role of Mn antioxidants in cells is sort of like oil in car engines. In cars, overheating and wear is prevented by air-cooling through mechanical radiators, and lubricant oils prevent heat by reducing friction. In this analogy, antioxidant enzymes are car radiators while Mn antioxidants, like engine oils, are widely distributed in cells and prevent burnout of the protein parts. Of course, a car with a broken radiator can run slowly, but not without oil, and this study shows that the same is true for Mn antioxidants in cells.
The team of researchers from USU, in collaboration with Northwestern University, applied an advanced spectroscopy technique called EPR, or electron paramagnetic resonance. They showed that the Mn antioxidant content within living C. elegans worms is readily tracked by EPR and that it is the level of the non-enzymatic Mn antioxidants, not antioxidant enzymes, in the worms that govern how long they live and how radiation resistant they are. The team further considered an even more dramatic possible application for the use of EPR to monitor Mn antioxidant level in cells. Viewing C. elegans worms as surrogates for human tissues, the present results suggest a possible use of EPR to determine the radiosensitivity of cancer biopsies, which might assist in optimizing a radiation/chemotherapeutic regime for specifically attacking a particular tumor.
This project was supported by a Defense Threat Reduction Agency (DTRA) grant to Dr. Daly and a National Institutes of Health (NIH) grant to Dr. Hoffman. The team included Dr. Igor Shuryak, Center for Radiological Research at Columbia University, New York, NY; and international collaborators Dr. Cene Gostinčar at the University of Ljubljana, Slovenia, and Isabel H. Conze at the Institute for Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne (CECAD), Germany.
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About the Uniformed Services University of the Health Sciences: The Uniformed Services University of the Health Sciences, founded by an act of Congress in 1972, is the nation’s federal health sciences university and the academic heart of the Military Health System. USU students are primarily active-duty uniformed officers in the Army, Navy, Air Force and Public Health Service who receive specialized education in tropical and infectious diseases, TBI and PTSD, disaster response and humanitarian assistance, global health, and acute trauma care. USU also has graduate programs in oral biology, biomedical sciences and public health committed to excellence in research. The University's research program covers a wide range of areas important to both the military and public health. For more information about USU and its programs, visit www.usuhs.edu.
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