Blocking a common enzyme slows aging

By ELAINE CHIAO | February 1, 2018

Imagine the thousands of enzymes that are required to maintain a healthy and functional human body. It might be surprising to find that some of these enzymes are so evolutionarily significant that they are present in almost every animal species on Earth. One of these ubiquitous enzymes is known as RNA Polymerase III (RNA Pol III), which is indispensable for regulating the production of proteins.

Recently, a team of researchers from University College London (UCL), the University of Kent and University of Groningen was surprised to discover another function of RNA Pol III that was previously unknown — its involvement in aging.

The researchers noticed that adult flies and worms experienced, on average, a 10 percent increase in lifespan following a decrease in RNA Pol III levels in their bodies.

Danny Filer, a researcher at the UCL Institute of Healthy Aging and one of the first co-authors of the paper published in Nature, explained that RNA Pol III activity can have deleterious effects on stem cell function and even the animal’s survival. Thus, its activity must be properly reduced to the ideal scope.

“As Pol III has the same structure and function across species, we think its role in mammals, and humans, warrants investigation as it may lead to important therapies,” Filer said in a press release.

The promise of developing an age-resistant drug might appeal to many people, but unfortunately there is often not enough evidence to shed light on the fundamental properties and functions of these drugs. For example, the drug rapamycin acts as an immune suppressor and is known to prolong lifespan in mice and other animals, but not much is currently known about the biological nuances that guide this activity.

The discovery of this new function of RNA Pol III is especially exciting to scientists who are trying to study and better understand the mechanism of the pathway. From studying Pol III, they now know that Pol III induces the onset of aging through responding to a signal that is normally inhibited by rapamycin. Additionally, limiting Pol III activity has virtually the same physiological effect as treatment with rapamycin.

“If we can investigate this mechanism… we can develop targeted anti-aging therapies,” co-author Nazif Alic said in a press release.

How does the research team efficiently inhibit the activity of Pol III? It turns out that they utilized a variety of genetic techniques ranging from insertional mutagenesis to RNA mediated interference.

Yeast, flies and worms were perfect model organisms for this study, since they are three species that are distinctly different phylogenetically but all contain the common enzyme, RNA Pol III. Pol III can be inhibited in many parts of these organisms’ bodies, such as in the guts and intestines of flies and worms.

Jennifer Tullet, a researcher at the University of Kent, was amazed at how a straightforward genetic adjustment could potentially have such a significant impact on a species’ functions and conditions.

“Understanding more about the underlying molecules at work here promises new strategies for anti-aging therapies,” Tullet said in a press release.

For the future, the team is planning to expand their work on Pol III in order to better dissect and investigate its functions in an adult organism. Eventually the manipulation of Pol III activity could have long-term benefits on human health and longevity.

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