A Key Enzyme
A new study has been able to extend the lifespan of worms and flies by inhibiting RNA polymerase III (Pol III). Since the enzyme is common to all animal species, including humans, researchers hope the discovery could lead to groundbreaking new therapies.
Researchers have long known that Pol III plays a key role in cell growth and the production of proteins, but recent insights revealed that when its activity was reduced during adulthood, the survival of yeast cells (as well as the longevity of flies and worms) could be extended by an average of 10 percent.
"We’ve uncovered a fundamental role for Pol III in adult flies and worms: its activity negatively impacts stem cell function, gut health and the animal’s survival," commented first author Danny Filer of the UCL Institute of Healthy Ageing, in a press release. "When we inhibit its activity, we can improve all these. 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."
Yeast, flies, and worms were selected for the study as they are not closely related, but all bear the enzyme. Various techniques, including insertional mutagenesis and RNA mediated interference, were used to inhibit Pol III and observe the results.
When it was inhibited in the gut of flies and worms, they lived longer. This was also the case when it was inhibited in only the flies' intestinal stem cells.
The results of Pol III inhibition have been compared to reactions to the immune-suppressing drug rapamycin, which is taken by cancer patients and organ transplant recipients. The drug has previously been shown to extend the lifespan of dogs. This latest study could help researchers better understanding exactly how rapamycin actually works.
"We now think that Pol III promotes growth and accelerates aging in response to a signal inhibited by rapamycin and that inhibiting Pol III is sufficient to result in flies living longer as if they were given rapamycin," said co-author Dr. Nazif Alic. "If we can investigate this mechanism further and across a wider range of species, we can develop targeted antiaging therapies."
The rapamycin compound was first discovered on Easter Island and has since been used to create drugs capable of extending the lives of several species. However, there hasn't been a study of its effects on human subjects — at least not yet.
Gaining a further understanding of the mechanism behind rapamycin could certainly make the idea of a human trial more tenable. The team plans to continue their research into how inhibiting Pol III effects an adult organism, and why doing so results in a longer lifespan. An anti-aging pill is still a long way off, but this type of research could provide some key foundational knowledge.