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Pol III Inhibition Modestly Extends Life in Flies and Worms

As a general rule, a 10% extension of life in short-lived species is nothing of any great significance. There are an increasing number of methods shown to do this, such as the one noted here. Researchers have more than doubled the life span in flies and worms in a few different ways over the past twenty years, however, and where the effects of any given intervention can be compared with the results in humans, it has been found that short-lived species have a much greater plasticity of life span. The large gains of calorie restriction and growth hormone receptor loss of function observed in lower species don't occur in our own species. This should be broadly true for just about everything that involves manipulating the operation of metabolism to slow down the pace at which damage occurs, as near all of that arises from mechanisms related to calorie restriction and insulin or growth hormone metabolism.

One should probably view this sort of work through the lens of scientific interest in mapping and cataloging the way in which aging works at the detail level - why the pace of aging varies somewhat between individuals, which mechanisms are most important, and so forth. Acquisition of knowledge is everything, and application of knowledge to the production of methods of slowing aging in humans is an afterthought. If that was the primary goal, researchers would instead pursue strategies with a much greater expectation of gains in longevity, the potential rejuvenation therapies based on repair of the damage that causes aging.

The enzyme - RNA polymerase III (Pol III) - is present in most cells across all animal species, including humans. While it is known to be essential for making proteins and for cell growth, its involvement in ageing was unexplored until now. A study has found that the survival of yeast cells, and the lifespans of flies and worms were extended by an average of 10% following a modest reduction in Pol III activity in adulthood. "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. 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."

The effects of inhibiting Pol III were found to be comparable to the action of the immune-suppressing drug rapamycin, which has previously been shown to extend the lifespans of mice and many other animals. This discovery will help scientists understand the mechanism of action of drugs, such as rapamycin, that show promise for extending the lifespans of mammals. "Understandably, there's a lot of hype around drugs that extend lifespan and promote healthy ageing but very little is known about how they work, which is fundamental knowledge. We now think that Pol III promotes growth and accelerates ageing 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. If we can investigate this mechanism further and across a wider range of species, we can develop targeted antiaging therapies."

Yeast, flies and worms were used as model organisms as they are not closely related but all contain Pol III. Inhibiting Pol III in the guts of flies and worms, was sufficient to extend lifespan, and when Pol III was inhibited in flies' intestinal stem cells alone, they also lived longer. The team now plan on continuing their work on Pol III to understand its function in an adult organism, and hence shed light on how a reduction in its activity can extend lifespan.

Link: http://www.ucl.ac.uk/news/news-articles/1117/301117-worms-and-flies-live-longer

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