The RNA discovery that could slow disease and ageing
More than 30 years ago, Victor Ambros and Gary Ruvkun peered down a microscope to study the development of a tiny worm called Caenorhabditis elegans (C.elegans). The two scientists discovered a new way genes are regulated.
They found a tiny strand of RNA that didn’t make proteins but instead, controlled how much protein other genes make. These molecules called microRNAs, are now known to help fine-tune every cell process in the body, including in humans. This discovery would one day earn them the Nobel Prize in Physiology or Medicine 2024.
Building on that discovery, researchers from the Clem Jones Centre for Ageing Dementia Research at UQ's Queensland Brain Institute (QBI) have found that one of these microRNAs, called miR-71, helps protect the body from stress caused by damaged mitochondria. Mitochondria are tiny structures inside the cells that turn the food we eat into energy for the body.
Sending alarm signals through the body
Mitochondria are often called the cell’s power plants. They take nutrients from our food and turn them into energy that keeps us alive. But they also act like sensors, sending stress signals when something goes wrong. Normally, and in small doses, these alarms help the body correct itself and stay in balance. But as mitochondria age or become damaged, the alarms can get stuck in the ‘on’ position spreading stress signals throughout the body. Over time, this overreaction can worsen ageing and increase the risk of disease.
"Within our mitochondria there is DNA that accumulates mutations as we age, causing chronic mitochondrial dysfunction as we get older, which has been linked to many age-related diseases including neurodegeneration, cancer, dementia, and diabetes.
“It is no wonder that the biggest risk factors for many of these diseases is ageing itself, which has been proposed to be caused by mitochondria that deteriorate over time."
“What we’ve essentially found is a new function for a specific microRNA that helps to suppress or dampen the overactivation of chronic stress signals caused by mitochondrial DNA damage, which is a good thing.”
The QBI researchers found that when mitochondrial DNA is damaged, miR-71 binds to the messenger RNAs of stress signal genes, causing them to break down before they can spread alarm signals to other cells.
"The natural levels of this microRNA increases during ageing, suggesting that it might be responding to the fact that as ageing occurs, the mitochondria get more and more dysfunctional. In simple terms, miR-71 keeps the cells in check and stops the system from overreacting."
“It’s a bit like an anti-inflammatory but for mitochondrial stress. You shouldn’t have stress pathways chronically activated. They serve a purpose for short-term activation, but are detrimental when on for a long time.”
Professor Zuryn’s lab is now investigating how to not only manage these signals but also prevent the damage that causes them in the first place.
From worms to humans
Although worms and humans seem worlds apart, many of our cellular pathways are surprisingly similar, keeping the humble C. elegans at the forefront of scientific discovery. In worms, boosting miR-71 helped the animals stay healthy even when their mitochondria were chronically damaged.
“It’s likely that humans have the same version of this system,” he said. “If we can learn how to safely deliver microRNAs or activate similar ones in human cells, we might be able to reduce the damaging effects of chronic mitochondrial stress. It’s an exciting possibility for tackling age-related disorders.”
This paper was published in Nature Communications.
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