Vilified free radicals boost tissue healing and regeneration in tadpoles (and perhaps humans)
Researchers at the University of Manchester have found that Reactive Oxygen Species (ROS) – oxygen-containing free radicals that are commonly believed to be harmful to cells – actually play a vital role in the regeneration of the tails of tadpoles. The finding could have profound implications for the healing and regeneration of human tissue.
Free radicals are a group of highly reactive molecules. The radicals containing oxygen are collectively known as ROS, and play a predominant role in biological systems: they are involved in cell signaling and maintaining homeostasis but, when their concentration increases beyond a certain threshold, they are believed to be responsible for cell damage and, some suggest, even aging. As a result antioxidants, which suppress ROS, have almost become a synonym for good health.
But in recent years, evidence has been mounting to suggest that ROS may not be the bad guys after all. Just days ago, a paper by Professor James Watson – co-discoverer of the DNA's double-helix – was published that greatly re-evaluated the importance of free radicals, with the Nobel laureate going so far as to say that antioxidant supplements "may have caused more cancers than they have prevented."
Now, building on their previous work, a research group led by Professor Amaya at the University of Manchester has confirmed that in tadpoles, hydrogen peroxide (H2O2) – a very common free radical – is not only harmless to cells, but is actually the catalyst that makes it possible for tadpoles' tails to completely regenerate in less than a week.
With the aid of a fluorescent dye, Amaya and colleagues started by measuring the level of hydrogen peroxide as a tadpole's tail was regenerating. They were able to show that H2O2 levels swiftly increase following tail amputation and that the levels remained elevated throughout the tail regeneration process.
By itself, this was no definite proof – the hydrogen peroxide could have been a simple byproduct, and not the catalyst of cell regeneration. So, to assess its importance, the researchers limited ROS production in two different ways – first by using chemicals, including antioxidants, and then by removing a gene responsible for ROS production. In both cases, the regeneration process was inhibited and the tadpole tail did not grow back.
"Our research suggests that ROS are essential to initiate and sustain the regeneration response. We also found that ROS production is essential to activate Wnt signalling, which has been implicated in essentially every studied regeneration system, including those found in humans," says Amaya.
Next, the researchers will study the role of ROS in the healing and regenerative processes more closely, in the hope to apply their findings to human health. It is possible, in fact, that manipulating ROS levels in the body could improve our ability to heal and regenerate tissues better.
According to Amaya, ongoing research suggests that there may well be a Goldilocks zone of ideal ROS levels in the human body. When levels are too low, healing can't happen properly; when levels are too high, cellular destruction starts to ensue; but when the level is "just right," tissues regenerate at maximum speed.
A paper detailing the research was published in the latest issue of the journal Nature Cell Biology.