Worm Study Suggests Antioxidants can Extend Radiation Resistance

By News Release


A new study that examined the impact of intense gamma radiation in worms suggests that higher levels of antioxidants – particularly manganese antioxidants – could potentially extend one’s lifespan and radiation resistance.

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 study, “Small-Molecule Mn Antioxidants in Caenorhabditis elegans and Deinococcus radiodurans Supplant MnSOD Enzymes during Aging and Irradiation,” was published in mBio by researchers at the Uniformed Services University of the Health Sciences (USU), the nation’s federal health sciences university and the academic heart of the Military Health System. It 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.