Free radicals cause cellular damage, which has been implicated in many diseases associated with aging, however few truly effective treatments exist to prevent free radicals wreaking havoc on our bodies. While food and nutritional supplements often tout the benefits of antioxidants at combating free radicals, most clinical trials have failed to provide compelling evidence supporting these claims.
According to Dr. Martin Brand, a researcher at the Buck Institute for Research on Aging, in Novato, California, current free radical-fighting treatments may be too broad to have a significant impact on the reactive cellular components. “Rather than a sledgehammer that seeks to decrease the effects of free radicals, we’ve developed a scalpel that allows us to stop them from being produced in the first place,” said Brand.
The generation of free radicals occurs within the energy-producing organelles in the cell, the mitochondria. Despite being a normal part of cellular energetics, free radicals can cause damage to other parts of the cell, and seem to accumulate more in association with cellular stress, disease and aging.
As the generation of free radicals is intimately connected to the cell’s essential production of energy, the challenge for researchers has been to develop drugs that block free radical release without interfering with energy metabolism. In their search for a targeted drug capable of performing this function, Brand and his colleagues screened a library of 635,000 small molecules.
They identified a few small molecules which were targeted toward a specific site in the electron transport chain, thought to be a key producer of free radicals. The research was published in the journal, Cell Metabolism.
The researchers tested these small molecule drug candidates in cell culture, isolated hearts and living disease models. In a mouse heart model of ischemia, the compounds were able to protect the cells against reperfusion injury when the blood supply was returned to the oxygen-deprived organ.
“For the first time we can test the effects of free radical damage in Alzheimer’s, Parkinson’s, cancer, type 2 diabetes, macular degeneration – you name it,” said Brand. “It gives you a target, and a drug candidate to hit that target.
“We can start to answer questions that scientists have puzzled about for 50 years in terms of the specifics of oxidative damage. We now have a precise tool to find out if the theory is correct. We can go into a biological system, see specifically what free radicals do and take preliminary steps to stop it.”